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  • 1.
    Abdelrahim, Nada A.
    et al.
    Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, Nile University, Khartoum, Sudan.
    Mohamed, Nahla
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Fadl-Elmula, Imad M.
    Department of Pathology and Clinical Genetics, Faculty of Medicine, Al-Neelain University, Khartoum, Sudan; Assafa Academy, Kartoum, Sudan.
    Human herpes virus type-6 is associated with central nervous system infections in children in Sudan2022Ingår i: African Journal of Laboratory Medicine, ISSN 2225-2002, E-ISSN 2225-2010, Vol. 11, nr 1, artikel-id a1718Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Human herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan.

    Objective: We investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan.

    Methods: Febrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden.

    Results: Of 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9-40.8). The median number of virus copies was 281.3/PCR run (1 × 105 copies/mL CSF; range: 30-44 × 103 copies/PCR run [12 × 103 - 18 × 106 copies/mL CSF]). All positive patients presented with fever and vomiting; 86.0% had seizures. The male-to-female ratio was 1:1; 50.0% were toddlers, 42.0% infants and 8.0% teenagers. Most (83.0%) were admitted in the dry season and 17.0% in the rainy season. Cerebrospinal fluid leukocytosis was seen in 33.0%, CSF glucose levels were normal in 86.0% and low in 14.0%, and CSF protein levels were low in 14.0% and high in 43.0%.

    Conclusion: Among children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.

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  • 2.
    Abdelrahim, Nada Abdelghani
    et al.
    Department of Pathology-Medical Microbiology, Faculty of Medicine, University of Medical Sciences and Technology, Khartoum, Sudan.
    Mohamed, Nahla
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Fadl-Elmula, Imad Mohammed
    Department of Pathology & Clinical Genetics, Al-Neelain University & Assafa Academy, Khartoum, Sudan.
    Viral meningitis in Sudanese children: differentiation, etiology and review of literature2022Ingår i: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 101, nr 46, artikel-id e31588Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.

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  • 3. Affognon, Hippolyte
    et al.
    Mburu, Peter
    Hassan, Osama Ahmed
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Kingori, Sarah
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Sang, Rosemary
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ethnic groups' knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya2017Ingår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, nr 3, artikel-id e0005405Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities.

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  • 4.
    Ahlm, Clas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Vapalahti, O.
    University of Helsinki and Helsinki University Central Hospital Laboratory, Finland.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Seroprevalence of Sindbis virus and associated risk factors in northern Sweden2014Ingår i: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 142, nr 7, s. 1559-1565Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mosquito-borne Sindbis virus (SINV) cause disease characterized by rash, fever and arthritis which often leads to long-lasting arthralgia. To determine the seroprevalence of SINV and associated risk factors in northern Sweden, a randomly selected population aged between 25 and 74 years were invited to join the MONICA study. Serum from 1611 samples were analysed for specific IgG antibodies. Overall, 2·9% had IgG against SINV. More men (3·7%) than women (2·0%) were SINV seropositive (P = 0·047) and it was more common in subjects with a lower educational level (P = 0·013) and living in small, rural communities (P < 0·001). Seropositivity was associated with higher waist circumference (P = 0·1), elevated diastolic blood pressure (P = 0·037), and history of a previous stroke (P = 0·011). In a multiple logistic regression analysis, adjusting for known risk factors for stroke, seropositivity for SINV was an independent predictor of having had a stroke (odds ratio 4·3, 95% confidence interval 1·4–13·0,P = 0·011).

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  • 5.
    Ahlm, Clas
    et al.
    Infektionskliniken, Norrlands universitetssjukhus, Umeå, Sweden.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Missfall orsakades av det myggburna Rift Valley-feberviruset2016Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, nr 42, artikel-id EAUZArtikel i tidskrift (Övrigt vetenskapligt)
  • 6. Andersen, Petter I.
    et al.
    Krpina, Klara
    Ianevski, Aleksandr
    Shtaida, Nastassia
    Jo, Eunji
    Yang, Jaewon
    Koit, Sandra
    Tenson, Tanel
    Hukkanen, Veijo
    Anthonsen, Marit W.
    Bjoras, Magnar
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Windisch, Marc P.
    Zusinaite, Eva
    Kainov, Denis E.
    Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine2019Ingår i: Viruses, E-ISSN 1999-4915, Vol. 11, nr 10, artikel-id 964Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.

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  • 7.
    Baudin, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hossain, Delowar
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Importance of charge interactions in Rift Valley fever virus attachment to host cellsManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    The mosquito-borne Rift Valley fever virus (RVFV) cause disease in both humans and animals and can infect a large range of animals as well as humans. Many different cell types are infected both in vivo and in vitro. To enter a cell the virus needs to attach and enter, and this initial binding to the host cell surface could depend on both general mechanisms, and different specific receptors. Our aim was to characterize determinants for RVFV entry into its host cells.To examine RVFV attachment to host cells we based our experimental assay on RVF virus-like particles containing a reporter gene. The enveloped RVFV uses protruding glycoproteins (Gn and Gc) for attachment and entry and to investigate potential virus-cell surface interactions, the net surface charge of the glycoproteins was first calculated. The RVFV glycoprotein Gn had a predicted isoelectric point (pI) of 7.6 and a net positive charge of +6.9 at pH 7.0, suggesting a charge interaction between the Gn ectodomain and the negatively charged cell surface. RVFV Gc on the other hand, was highly negatively charged, -12.8 at neutral pH, most probably reflecting that Gc is not exposed until after receptor binding. To characterize the general conditions needed for RVFV attachment, cells or virus were treated with various compounds. Both sodium chloride and the negatively charged heparin inhibited RVF virus-like particle infection, strongly indicating that viral binding was charge-dependent. Treatment with sodium periodate pointed to a carbohydrate structure as a cellular interaction partner. Removal of sialic acid or heparan sulfate receptors on the cell surface by enzymatic treatment and blocking of the heparan sulfate receptor did not inhibit virus attachment.In conclusion, RVFV binding to host cells was charge dependent and the results point to a carbohydrate structure with negative charge as a potential attachment factor.

  • 8.
    Baudin, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Jumaa, Ammar M.
    Jomma, Huda J. E.
    Karsany, Mubarak S.
    Bucht, Göran
    Näslund, Jonas
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Mohamed, Nahla
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Association of Rift Valley fever virus infection with miscarriage in Sudanese women: a cross-sectional study2016Ingår i: The Lancet Global Health, E-ISSN 2214-109X, Vol. 4, nr 11, s. e864-e871Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Rift Valley fever virus is an emerging mosquito-borne virus that causes infections in animals and human beings in Africa and the Arabian Peninsula. Outbreaks of Rift Valley fever lead to mass abortions in livestock, but such abortions have not been identified in human bezings. Our aim was to investigate the cause of miscarriages in febrile pregnant women in an area endemic for Rift Valley fever.

    METHODS: Pregnant women with fever of unknown origin who attended the governmental hospital of Port Sudan, Sudan, between June 30, 2011, and Nov 17, 2012, were sampled at admission and included in this cross-sectional study. Medical records were retrieved and haematological tests were done on patient samples. Presence of viral RNA as well as antibodies against a variety of viruses were analysed. Any association of viral infections, symptoms, and laboratory parameters to pregnancy outcome was investigated using Pearson's χ(2) test.

    FINDINGS: Of 130 pregnant women with febrile disease, 28 were infected with Rift Valley fever virus and 31 with chikungunya virus, with typical clinical and laboratory findings for the infection in question. 15 (54%) of 28 women with an acute Rift Valley fever virus infection had miscarriages compared with 12 (12%) of 102 women negative for Rift Valley fever virus (p<0·0001). In a multiple logistic regression analysis, adjusting for age, haemorrhagic disease, and chikungunya virus infection, an acute Rift Valley fever virus infection was an independent predictor of having a miscarriage (odds ratio 7·4, 95% CI 2·7-20·1; p<0·0001).

    INTERPRETATION: This study is the first to show an association between infection with Rift Valley fever virus and miscarriage in pregnant women. Further studies are warranted to investigate the possible mechanisms. Our findings have implications for implementation of preventive measures, and evidence-based information to the public in endemic countries should be strongly recommended during Rift Valley fever outbreaks.

    FUNDING: Schlumberger Faculty for the Future, CRDF Global (31141), the Swedish International Development Cooperation Agency, the County Council of Västerbotten, and the Faculty of Medicine, Umeå University.

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  • 9.
    Bergqvist, Joakim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Forsman, Oscar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Larsson, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Näslund, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Lilja, Tobias
    Engdahl, Cecilia
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindström, Anders
    Gylfe, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Bucht, Göran
    [ 1 ] CBRN Def & Secur, Swedish Def Res Agcy, SE-90182 Umea, Sweden.
    Detection and Isolation of Sindbis Virus from Mosquitoes Captured During an Outbreak in Sweden, 20132015Ingår i: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 15, nr 2, s. 133-140Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mosquito-borne alphaviruses have the potential to cause large outbreaks throughout the world. Here we investigated the causative agent of an unexpected Sindbis virus (SINV) outbreak during August-September, 2013, in a previously nonendemic region of Sweden. Mosquitoes were collected using carbon dioxide-baited CDC traps at locations close to human cases. The mosquitoes were initially screened as large pools by SINV-specific quantitative RT-PCR, and the SINV-positive mosquitoes were species determined by single-nucleotide polymorphism (SNP) analysis, followed by sequencing the barcoding region of the cytochrome oxidase I gene. The proportion of the collected mosquitoes was determined by a metabarcoding strategy. By using novel strategies for PCR screening and genetic typing, a new SINV strain, Lovanger, was isolated from a pool of 1600 mosquitoes composed of Culex, Culiseta, and Aedes mosquitoes as determined by metabarcoding. The SINV-positive mosquito Culiseta morsitans was identified by SNP analysis and sequencing. After whole-genome sequencing and phylogenetic analysis, the SINV Lovanger isolate was shown to be most closely similar to recent Finnish SINV isolates. In conclusion, within a few weeks, we were able to detect and isolate a novel SINV strain and identify the mosquito vector during a sudden SINV outbreak.

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  • 10.
    Bergstedt Oscarsson, Kristina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Brorstad, Alette
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Baudin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Forssén, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Human Puumala hantavirus infection in northern Sweden: increased seroprevalence and association to risk and health factors2016Ingår i: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 16, artikel-id 566Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The rodent borne Puumala hantavirus (PUUV) causes haemorrhagic fever with renal syndrome in central and northern Europe. The number of cases has increased and northern Sweden has experienced large outbreaks in 1998 and 2006-2007 which raised questions regarding the level of immunity in the human population.

    METHODS: A randomly selected population aged between 25 and 74 years from northern Sweden were invited during 2009 to participate in a WHO project for monitoring of trends and determinants in cardiovascular disease. Health and risk factors were evaluated and sera from 1,600 participants were available for analysis for specific PUUV IgG antibodies using a recombinant PUUV nucleocapsid protein ELISA.

    RESULTS: The overall seroprevalence in the investigated population was 13.4 %, which is a 50 % increase compared to a similar study only two decades previously. The prevalence of PUUV IgG increased with age, and among 65-75 years it was 22 %. More men (15.3 %) than women (11.4 %) were seropositive (p < 0.05). The identified risk factors were smoking (OR = 1.67), living in rural areas (OR = 1.92), and owning farmland or forest (OR = 2.44). No associations were found between previous PUUV exposure and chronic lung disease, diabetes, hypertension, renal dysfunction, stroke or myocardial infarction.

    CONCLUSIONS: PUUV is a common infection in northern Sweden and there is a high life time risk to acquire PUUV infection in endemic areas. Certain risk factors as living in rural areas and smoking were identified. Groups with increased risk should be targeted for future vaccination when available, and should also be informed about appropriate protection from rodent secreta.

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  • 11.
    Bergstedt-Oskarsson, Kristina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Brorstad, Alette
    Baudin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lindberg, Anne
    Forssén, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Seroepidemiology, comorbidity and riskfactors for Puumula hantavirus in a highly endemic area of Sweden2011Konferensbidrag (Övrigt vetenskapligt)
  • 12. Björkström, Niklas K
    et al.
    Lindgren, Therese
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Stoltz, Malin
    Fauriat, Cyril
    Braun, Monika
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Michaëlsson, Jakob
    Malmberg, Karl-Johan
    Klingström, Jonas
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Ljunggren, Hans-Gustaf
    Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus2011Ingår i: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 208, nr 1, s. 13-21Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Natural killer (NK) cells are known to mount a rapid response to several virus infections. In experimental models of acute viral infection, this response has been characterized by prompt NK cell activation and expansion followed by rapid contraction. In contrast to experimental model systems, much less is known about NK cell responses to acute viral infections in humans. We demonstrate that NK cells can rapidly expand and persist at highly elevated levels for >60 d after human hantavirus infection. A large part of the expanding NK cells expressed the activating receptor NKG2C and were functional in terms of expressing a licensing inhibitory killer cell immunoglobulin-like receptor (KIR) and ability to respond to target cell stimulation. These results demonstrate that NK cells can expand and remain elevated in numbers for a prolonged period of time in humans after a virus infection. In time, this response extends far beyond what is considered normal for an innate immune response.

  • 13.
    Drobni, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Mistry, Nitesh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    McMillan, Nigel
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Carboxy-fluorescein diacetate, succinimidyl ester labeled papillomavirus virus-like particles fluoresce after internalization and interact with heparan sulfate for binding and entry2003Ingår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 310, nr 1, s. 163-172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human papillomaviruses (HPVs) infect epithelial cells and are associated with genital carcinoma. Most epithelial cell lines express cell-surface glycosaminoglycans (GAGs) usually found attached to the protein core of proteoglycans. Our aim was to study how GAGs influenced HPV entry. Using a human keratinocyte cell line (HaCaT), preincubation of HPV virus-like particles (VLPs) with GAGs showed a dose-dependent inhibition of binding. The IC(50) (50% inhibition) was only 0.5 microg/ml for heparin, 1 microg/ml for dextran sulfate, and 5-10 microg/ml for heparan sulfate from mucosal origin. Mutated chinese hamster ovary (CHO) cell lines lacking heparan sulfate or all GAGs were unable to bind HPV VLPs. Here we also report a method to study internalization by using VLPs labeled with carboxy-fluorescein diacetate, succinimidyl ester, a fluorochrome that is only activated after cell entry. Pretreatment of labeled HPV VLPs with heparin inhibited uptake, suggesting a primary interaction between HPV and cell-surface heparan sulfate.

  • 14.
    Drobni, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Näslund, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lactoferrin inhibits human papillomavirus binding and uptake in vitro.2004Ingår i: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 64, nr 1, s. 63-68Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lactoferrin (LF), a member of the transferrin family, is a bi-globular protein secreted in milk, saliva, tears, seminal fluid, endocervix and vaginal secretions. LF is an important player in the defence against pathogenic microorganisms and has also been shown to have activity against several viruses including herpesvirus, adenovirus, rotavirus and poliovirus. The antiviral activity of LF is directed against the early steps of viral infection and the LF antiviral effect against herpesvirus is mediated through LF binding to the herpesvirus receptor heparan sulfate. Human papillomavirus (HPV) causes genital warts and is a prerequisite for cervical cancer. HPV can also use heparan sulfate on the cell surface as a receptor. We studied the inhibition by LF on HPV entry by incubating HaCaT cells and HPV-16 virus-like particles (VLPs) with either human (HLF) or bovine lactoferrin (BLF). LF inhibited internalization of HPV-16 particles using CFDA-SE-labelled VLPs that only fluoresce after internalisation. By using a western blot assay we also found dose-dependent LF inhibition of HPV-16 VLP binding to the HaCaT cell surface. BLF was a more potent inhibitor of HPV entry than human LF. It was also clear that LF acted early in the HPV uptake process.

  • 15.
    Drobni, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Näslund, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Jenssen, Håvard
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    The anti-HPV activity of human and bovine lactoferricin.Manuskript (Övrigt vetenskapligt)
  • 16.
    Ecke, Frauke
    et al.
    Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Khalil, Hussein
    Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Magnusson, Magnus
    Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Niklasson, Bo
    Jordbro Primary Health Care Center, Stockholm, Sweden.
    Singh, Navinder J.
    Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Hörnfeldt, Birger
    Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Puumala Orthohantavirus Infection Does Not Affect the Trapping Success of Its Reservoir Host2022Ingår i: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 22, nr 5, s. 297-299Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pathogens might affect behavior of infected reservoir hosts and hence their trappability, which could bias population estimates of pathogen prevalence. In this study, we used snap-trapping data on Puumala orthohantavirus (PUUV)-infected (n = 1619) and noninfected (n = 6940) bank voles (Myodes glareolus) from five vole cycles, normally representing increase, peak, and decline phase, to evaluate if infection status affected trapping success. If PUUV infection, as previously suggested, increases activity and/or mobility, we would expect a higher proportion of infected than noninfected specimens in the first trapping night. However, the proportion of PUUV-infected voles did not differ across the three trapping nights. We conclude that PUUV infection did not affect trapping success, confirming snap trapping as an appropriate trapping method for studies on PUUV prevalence and likely other orthohantaviruses.

  • 17.
    Ecke, Frauke
    et al.
    Department of Wildlife, Fish, and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Magnusson, Magnus
    Department of Wildlife, Fish, and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden; Swedish Forest Agency, Umeå, Sweden.
    Han, Barbara A.
    Cary Institute of Ecosystem Studies, NY, Millbrook, United States.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Orthohantaviruses in the Arctic: present and future2022Ingår i: Arctic one health: challenges for northern animals and people / [ed] Morten Tryland, Springer, 2022, s. 393-414Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    Orthohantaviruses, family Hantaviridae, are globally distributed except for Antarctica where they are absent. In animals, orthohantaviruses are transmitted horizontally, either directly through aggressive interactions and grooming or by inhaling infectious particles shed from urine, feces, or saliva in the environment. Humans become infected by inhaling aerosols of the virus-contaminated excretions of small mammals. Orthohantaviral infections in humans cause severe hantavirus pulmonary syndrome (HPS) in the North American Artic and hemorrhagic fever with renal syndrome (HFRS) in the Eurasian Arctic. In the Arctic, 16 rodent species (order Rodentia) and five shrew species (order Eulipotyphla) have been identified as reservoirs of orthohantaviruses by RNA detection. The two most important reservoir rodents in the Arctic are the bank vole (Myodes glareolus) in Eurasia carrying Puumala orthohantavirus (PUUV) and North American deermouse (Peromyscus maniculatus) in the North American Arctic carrying Sin Nombre orthohantavirus (SNV); both rodents being habitat generalists occurring in natural and human-modified habitats. Global warming, either independently or in combination with onshore exploitation of natural resources, is expected to increase the distribution range of reservoirs (including bank vole and North American deermouse, rats (Rattus rattus and R. norvegicus), house mouse (Mus musculus) and field mice (Apodemus spp.)), and their associated orthohantaviruses. These changes pose the risk of introducing New World orthohantaviruses (e.g., Jemez Springs virus (JMSV) and SNV) to areas where so far only Old World orthohantaviruses (e.g., Hantaan orthohantavirus (HTNV) and PUUV) occur and vice versa. Climate change in the Arctic will likely also promote transmission and prevalence of orthohantaviruses in their reservoirs and hence increase zoonotic risk. The expected environmental changes call for increased surveillance and preparedness to mitigate potential outbreaks of orthohantavirus diseases in humans.

  • 18. Ecke, Frauke
    et al.
    Mahani, Seyed Alireza Nematollahi
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Hörnfeldt, Birger
    Khalil, Hussein
    Wildfire-induced short-term changes in a small mammal community increase prevalence of a zoonotic pathogen?2019Ingår i: Ecology and Evolution, E-ISSN 2045-7758, Vol. 9, nr 22, s. 12459-12470Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Natural disturbances like droughts and fires are important determinants of wildlife community structure and are suggested to have important implications for prevalence of wildlife-borne pathogens. After a major wildfire affecting >1,600 ha of boreal forest in Sweden in 2006, we took the rare opportunity to study the short-term response (2007-2010 and 2015) of small mammal community structure, population dynamics, and prevalence of the Puumala orthohantavirus (PUUV) hosted by bank voles (Myodes glareolus). We performed snap-trapping in permanent trapping plots in clear-cuts (n = 3), unburnt reference forests (n = 7), and the fire area (n = 7) and surveyed vegetation and habitat structure. Small mammal species richness was low in all habitats (at maximum three species per trapping session), and the bank vole was the only small mammal species encountered in the fire area after the first postfire year. In autumns of years of peak rodent densities, the trapping index of bank voles was lowest in the fire area, and in two of three peak-density years, it was highest in clear-cuts. Age structure of bank voles varied among forest types with dominance of overwintered breeders in the fire area in the first postfire spring. PUUV infection probability in bank voles was positively related to vole age. Infection probability was highest in the fire area due to low habitat complexity in burnt forests, which possibly increased encounter rate among bank voles. Our results suggest that forest fires induce cascading effects, including fast recovery/recolonization of fire areas by generalists like bank voles, impoverished species richness of small mammals, and altered prevalence of a rodent-borne zoonotic pathogen. Our pilot study suggests high human infection risk upon encountering a bank vole in the fire area, however, with even higher overall risk in unburnt forests due to their higher vole numbers.

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  • 19.
    Engdahl, Cecilia
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Larsson, Pär
    Swedish Defense Research Agency, CBRN Defense and Security, Umeå, Sweden.
    Näslund, Jonas
    Swedish Defense Research Agency, CBRN Defense and Security, Umeå, Sweden.
    Bravo, Mayra
    Swedish Defense Research Agency, CBRN Defense and Security, Umeå, Sweden.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lundström, Jan O.
    Department of Ecology and Genetics, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Bucht, Göran
    Swedish Defense Research Agency, CBRN Defense and Security, Umeå, Sweden.
    Identification of Swedish mosquitoes based on molecular barcoding of the COI gene and SNP analysis2014Ingår i: Molecular Ecology Resources, ISSN 1755-098X, E-ISSN 1755-0998, Vol. 14, nr 3, s. 478-488Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mosquito-borne infectious diseases are emerging in many regions of the world. Consequently, surveillance of mosquitoes and concomitant infectious agents is of great importance for prediction and prevention of mosquito-borne infectious diseases. Currently, morphological identification of mosquitoes is the traditional procedure. However, sequencing of specified genes or standard genomic regions, DNA barcoding, has recently been suggested as a global standard for identification and classification of many different species. Our aim was to develop a genetic method to identify mosquitoes and to study their relationship. Mosquitoes were captured at collection sites in northern Sweden and identified morphologically before the cytochrome c oxidase subunit I (COI) gene sequences of 14 of the most common mosquito species were determined. The sequences obtained were then used for phylogenetic placement, for validation and benchmarking of phenetic classifications and finally to develop a hierarchical PCR-based typing scheme based on single nucleotide polymorphism sites (SNPs) to enable rapid genetic identification, circumventing the need for morphological characterization. The results showed that exact phylogenetic relationships between mosquito taxa were preserved at shorter evolutionary distances, but at deeper levels, they could not be inferred with confidence using COI gene sequence data alone. Fourteen of the most common mosquito species in Sweden were identified by the SNP/PCR-based typing scheme, demonstrating that genetic typing using SNPs of the COI gene is a useful method for identification of mosquitoes with potential for worldwide application.

  • 20.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Detection of human papillomavirus: a study of normal cells, cervical intraepithelial neoplasia and cancer of the uterine cervix1991Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Human papillomavirus (HPV) infections of the genital tract are now recognized to be among the most prevalent sexually transmitted diseases and also a contributing factor to some cancers of the lower genital tract of women and men. Presence of HPV in a clinical specimen is confined to detection of the HPV genome by DNA hybridization techniques.

    In this thesis, the commonly used DNA hybridization techniques Southern blot and filter in situ hybridization (FISH), were first used for detection of genital HPV infection. In order to increase and simplify the detection of HPV in clinical specimens a more sensitive technique, the polymerase chain reaction (PCR) was subsequently utilized.

    For type-specific amplificaiton of HPV 6, 16, 18 and 33 by PCR, oligonucleotide primers located in the E6 and E7 regions of the HPV genome were selected. They were found to specifically amplify the four types. To be able to amplify a broad spectrum of genital HPV types, general primers located in the E7 and El region of the HPV genome, were designed and evaluated. They were found to amplify a wide range of genital HPV types. To further increase the sensitivity and specificity, a two-step PCR using general primers, was assembled and evaluated against a one-step PCR on cervical scrapes from young women in a population-based study. The two-step PCR increased the sensitivity about three-fold compared to the one-step PCR.

    By Southern blot and FISH, 46% of women with abnormal Papanicolaou (Pap) smears were shown to carry HPV DNA. Of the women analysed by Southern blot, 39 % harboured HPV DNA and 25 % proved HPV 16 positive. Of the samples analysed with FISH, 27 % contained HPV DNA, compared to 11 % of samples from a group of reference women with normal cytology. With the Southern blot technique, HPV DNA was detected in 66% of women with cervical intraepithelial neoplasia grade III (CIN III) lesions. Fifty-four percent of the women with CIN III lesions were positive for HPV 16 DNA.

    By type-specific PCR, 12 out of 13 women with cervical squamous carcinoma were shown to carry HPV 16 and/or 18. Among women with adenosquamous carcinoma of the cervix, HPV 18 was the most prevalent type (26%) but HPV 16 was also found in a proportion of the women(15 %). Nine of 13 premenopausal cases with cervical adenocarcinoma were HPV positive compared to only 2 of 13 postmenopausal cases (p< 0.015). HPV 16 DNA was detected in 48%of women with cervical intraepithelial neoplasia (CIN), by the use of type-specific PCR.

    Three different groups of women with normal cytology were studied. Among women attending a family planning clinic in Kenya, 19% were shown to carry HPV virus, by the use of general primers. HPV 16 was found in 5.2% of these women and HPV 18 in 3.9%. In anothergroup of women, attending the gynecological department in Umeå, HPV 16 DNA was detected in 21 % by type-specific PCR. However, if consideration was taken to the medical status of the women, only 10% of women without any medical history were HPV 16 DNA positive, versus 54% of women with diseases and women with a relative progesterone dominance. Finally, by use of a two-step PCR using general primers, 20% of young women from Umeå taking part in a population-based study were demonstrated to carry HPV DNA. The most prevalent types were HPV 6 (2.0%) and HPV 16(2.7%). Among the women in this study with normal cytology, 19%were HPV positive.

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  • 21.
    Evander, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Milder winters in northern Scandinavia may contribute to larger outbreaks of haemorrhagic fever virus2009Ingår i: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The spread of zoonotic infectious diseases may increase due to climate factors such as temperature, humidity and precipitation. This is also true for hantaviruses, which are globally spread haemorrhagic fever viruses carried by rodents. Hantaviruses are frequently transmitted to humans all over the world and regarded as emerging viral diseases. Climate variations affect the rodent reservoir populations and rodent population peaks coincide with increased number of human cases of hantavirus infections. In northern Sweden, a form of haemorrhagic fever called nephropathia epidemica (NE), caused by the Puumala hantavirus (PUUV) is endemic and during 2006-2007 an unexpected, sudden and large outbreak of NE occurred in this region. The incidence was 313 cases/100,000 inhabitants in the most endemic areas, and from January through March 2007 the outbreak had a dramatic and sudden start with 474 cases in the endemic region alone. The PUUV rodent reservoir is bank voles and immediately before and during the peak of disease outbreak the affected regions experienced extreme climate conditions with a record-breaking warm winter, registering temperatures 6-9 degrees C above normal. No protective snow cover was present before the outbreak and more bank voles than normal came in contact with humans inside or in close to human dwellings. These extreme climate conditions most probably affected the rodent reservoir and are important factors for the severity of the outbreak.

  • 22.
    Evander, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Eriksson, Irene
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Pettersson, Lisa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Olsson, Gert E
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Bucht, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Allard, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Puumala hantavirus viremia diagnosed by real-time reverse transcriptase PCR using samples from patients with hemorrhagic fever and renal syndrome2007Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 45, nr 8, s. 2491-2497Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Puumala virus (PUUV) is the endemic hantavirus in northern Sweden and causes nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome. There is a need for fast and reliable diagnostics to differentiate the disease from other infections. By aligning virus RNA sequences isolated from 11 different bank voles and one human patient, we designed a real-time reverse transcriptase (RT) PCR method for detection of PUUV RNA. The real-time RT-PCR assay showed linearity from 20 to 2 x 10(6) virus copies with a correlation coefficient above 0.98 to 0.99 for all experiments. The detection threshold for PUUV cDNA was two copies per reaction. A two-step qualitative RT-PCR to detect PUUV RNA showed 100% concordance with the real-time RT-PCR assay. PUUV RNA viremia was detected in 33 of 34 PUUV immunoglobulin M (IgM)-positive patients with typical clinical NE disease from the region of endemicity. One PUUV IgM-negative sample had PUUV RNA, and 4 days later, the patient was IgM positive. Of samples with indeterminate IgM, 43% were PUUV RNA positive. The kinetics of antibody titers and PUUV viremia were studied, and five of six NE patients displayed a decrease in PUUV viremia a few days after disease outbreak coupled with an increase in PUUV IgM and IgG. In one patient with continuously high PUUV RNA levels but low IgM and no IgG response, the infection was lethal. These findings demonstrated that real-time RT-PCR is a useful method for diagnosis of PUUV viremia and for detecting PUUV RNA at early time points, before the appearance of IgM antibodies.

  • 23.
    Evander, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Putkuri, Niina
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lwande, Olivia Wesula
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Vapalahti, Olli
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Seroprevalence and Risk Factors of Inkoo Virus in Northern Sweden2016Ingår i: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 94, nr 5, s. 1103-1106Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The mosquito-borne Inkoo virus (INKV) is a member of the California serogroup in the family Bunyaviridae, genus Orthobunyavirus These viruses are associated with fever and encephalitis, although INKV infections are not usually reported and the incidence is largely unknown. The aim of the study was to determine the prevalence of anti-INKV antibodies and associated risk factors in humans living in northern Sweden. Seroprevalence was investigated using the World Health Organization Monitoring of Trends and Determinants in Cardiovascular Disease study, where a randomly selected population aged between 25 and 74 years (N = 1,607) was invited to participate. The presence of anti-INKV IgG antibodies was determined by immunofluorescence assay. Seropositivity for anti-INKV was significantly higher in men (46.9%) than in women (34.8%; P < 0.001). In women, but not in men, the prevalence increased somewhat with age (P = 0.06). The peak in seropositivity was 45-54 years for men and 55-64 years for women. Living in rural areas was associated with a higher seroprevalence. In conclusion, the prevalence of anti-INKV antibodies was high in northern Sweden and was associated with male sex, older age, and rural living. The age distribution indicates exposure to INKV at a relatively early age. These findings will be important for future epidemiological and clinical investigations of this relatively unknown mosquito-borne virus.

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  • 24.
    Gwon, Yong-Dae
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Strand, Mårten
    Lindquist, Richard
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Nilsson, Emma
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Saleeb, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Elofsson, Mikael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Överby, Anna K.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Antiviral Activity of Benzavir-2 against Emerging Flaviviruses2020Ingår i: Viruses, E-ISSN 1999-4915, Vol. 12, nr 3, artikel-id 351Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 +/- 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses: WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.

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  • 25. Hardestam, Jonas
    et al.
    Petterson, Lisa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lundkvist, Ake
    Klingström, Jonas
    Antiviral effect of human saliva against hantavirus.2008Ingår i: Journal of medical virology, ISSN 1096-9071, Vol. 80, nr 12, s. 2122-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome are zoonotic diseases caused by rodent borne hantaviruses. Transmission to humans occurs usually by inhalation of aerozolized virus-contaminated rodent excreta. Although human-to-human transmission of Andes hantavirus has been observed, the mode of transmission is currently not known. Saliva from Puumala hantavirus (PUUV)-infected patients was shown recently to contain viral RNA. To test if human saliva interferes with hantavirus replication, the effect of saliva and salivary proteins on hantavirus replication was studied. It was observed that saliva from healthy individuals reduced Hantaan hantavirus (HTNV) infectivity, although not completely. Furthermore, HTNV was resistant against the antiviral capacity of histatin 5, lysozyme, lactoferrin, and SLPI, but was inhibited by mucin. Inoculation of bank voles (Myodes glareolus) with HFRS-patient saliva, positive for PUUV-RNA, did not induce sero-conversion. In conclusion, no evidence of infectious virus in patient saliva was found. However, the in vitro experiments showed that HTNV, the prototype hantavirus, is insensitive to several antiviral salivary proteins, and is partly resistant to the antiviral effect of saliva. It therefore remains to be shown if human saliva might contain infectious virions early during infection, that is, before seroconversion.

  • 26.
    Hassan, Osama Ahmed
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Public Health Institute, Khartoum, Sudan.
    Affognon, Hippolyte
    Rocklöv, Joacim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Mburu, Peter
    Sang, Rosemary
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    The One Health approach to identify knowledge, attitudes and practices that affect community involvement in the control of Rift Valley fever outbreaks2017Ingår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, nr 2, artikel-id e0005383Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rift Valley fever (RVF) is a viral mosquito-borne disease with the potential for global expansion, causes hemorrhagic fever, and has a high case fatality rate in young animals and in humans. Using a cross-sectional community-based study design, we investigated the knowledge, attitudes and practices of people living in small village in Sudan with respect to RVF outbreaks. A special One Health questionnaire was developed to compile data from 235 heads of household concerning their knowledge, attitudes, and practices with regard to controlling RVF. Although the 2007 RVF outbreak in Sudan had negatively affected the participants' food availability and livestock income, the participants did not fully understand how to identify RVF symptoms and risk factors for both humans and livestock. For example, the participants mistakenly believed that avoiding livestock that had suffered spontaneous abortions was the least important risk factor for RVF. Although the majority noticed an increase in mosquito population during the 2007 RVF outbreak, few used impregnated bed nets as preventive measures. The community was reluctant to notify the authorities about RVF suspicion in livestock, a sentinel for human RVF infection. Almost all the respondents stressed that they would not receive any compensation for their dead livestock if they notified the authorities. In addition, the participants believed that controlling RVF outbreaks was mainly the responsibility of human health authorities rather than veterinary authorities. The majority of the participants were aware that RVF could spread from one region to another within the country. Participants received most their information about RVF from social networks and the mass media, rather than the health system or veterinarians. Because the perceived role of the community in controlling RVF was fragmented, the probability of RVF spread increased.

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  • 27.
    Hassan, Osama Ahmed
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. Department of Epidemiology and Diseases Control, Public Health Institute, Federal Ministry of Health, Khartoum, Sudan.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    A need for One Health approach: lessons learned from outbreaks of Rift Valley fever in Saudi Arabia and Sudan2014Ingår i: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 4, artikel-id 20710Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Rift Valley fever (RVF) is an emerging viral zoonosis that impacts human and animal health. It is transmitted from animals to humans directly through exposure to blood, body fluids, or tissues of infected animals or via mosquito bites. The disease is endemic to Africa but has recently spread to Saudi Arabia and Yemen. Our aim was to compare two major outbreaks of RVF in Saudi Arabia (2000) and Sudan (2007) from a One Health perspective.

    METHODS: Using the terms 'Saudi Arabia', 'Sudan', and 'RVF', articles were identified by searching PubMed, Google Scholar, and web pages of international organizations as well as local sources in Saudi Arabia and Sudan.

    RESULTS: The outbreak in Saudi Arabia caused 883 human cases, with a case fatality rate of 14% and more than 40,000 dead sheep and goats. In Sudan, 698 human cases of RVF were recognized (case fatality, 31.5%), but no records of affected animals were available. The ecology and environment of the affected areas were similar with irrigation canals and excessive rains providing an attractive habitat for mosquito vectors to multiply. The outbreaks resulted in livestock trade bans leading to a vast economic impact on the animal market in the two countries. The surveillance system in Sudan showed a lack of data management and communication between the regional and federal health authorities, while in Saudi Arabia which is the stronger economy, better capacity and contingency plans resulted in efficient countermeasures. Studies of the epidemiology and vectors were also performed in Saudi Arabia, while in Sudan these issues were only partly studied.

    CONCLUSION: We conclude that a One Health approach is the best option to mitigate outbreaks of RVF. Collaboration between veterinary, health, and environmental authorities both on national and regional levels is needed.

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  • 28.
    Hassan, Osama Ahmed
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. Federal Ministry of Health, Khartoum, Sudan.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Sang, Rosemary
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    The 2007 rift valley Fever outbreak in Sudan2011Ingår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 5, nr 9, artikel-id e1229Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of animals. The virus is transmitted through bites from mosquitoes and exposure to viremic blood, body fluids, or tissues of infected animals. During 2007 a large RVF outbreak occurred in Sudan with a total of 747 confirmed human cases including 230 deaths (case fatality 30.8%); although it has been estimated 75,000 were infected. It was most severe in White Nile, El Gezira, and Sennar states near to the White Nile and the Blue Nile Rivers. Notably, RVF was not demonstrated in livestock until after the human cases appeared and unfortunately, there are no records or reports of the number of affected animals or deaths. Ideally, animals should serve as sentinels to prevent loss of human life, but the situation here was reversed. Animal contact seemed to be the most dominant risk factor followed by animal products and mosquito bites. The Sudan outbreak followed an unusually heavy rainfall in the country with severe flooding and previous studies on RVF in Sudan suggest that RVFV is endemic in parts of Sudan. An RVF outbreak results in human disease, but also large economic loss with an impact beyond the immediate influence on the directly affected agricultural producers. The outbreak emphasizes the need for collaboration between veterinary and health authorities, entomologists, environmental specialists, and biologists, as the best strategy towards the prevention and control of RVF.

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  • 29. Hoffman, Tove
    et al.
    Lindeborg, Mats
    Barboutis, Christos
    Erciyas-Yavuz, Kiraz
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Fransson, Thord
    Figuerola, Jordi
    Jaenson, Thomas G. T.
    Kiat, Yosef
    Lindgren, Per-Eric
    Lundkvist, Åke
    Mohamed, Nahla
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Moutailler, Sara
    Nyström, Fredrik
    Olsen, Björn
    Salaneck, Erik
    Alkhurma Hemorrhagic Fever Virus RNA in Hyalomma rufipes Ticks Infesting Migratory Birds, Europe and Asia Minor2018Ingår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, nr 5, s. 879-882Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alkhurma hemorrhagic fever virus RNA was detected in immature Hyalomma rufipes ticks infesting northward migratory birds caught in the North Mediterranean Basin. This finding suggests a role for birds in the ecology of the Alkhurma hemorrhagic fever virus and a potential mechanism for dissemination to novel regions. Increased surveillance is warranted.

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  • 30. Ianevski, Aleksandr
    et al.
    Zusinaite, Eva
    Kuivanen, Suvi
    Strand, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lysvand, Hilde
    Teppor, Mona
    Kakkola, Laura
    Paavilainen, Henrik
    Laajala, Mira
    Kallio-Kokko, Hannimari
    Valkonen, Miia
    Kantele, Anu
    Telling, Kaidi
    Lutsar, Irja
    Letjuka, Pille
    Metelitsa, Natalja
    Oksenych, Valentyn
    Bjoras, Magnar
    Nordbo, Svein Arne
    Dumpis, Uga
    Vitkauskiene, Astra
    Ohrmalm, Christina
    Bondeson, Kare
    Bergqvist, Anders
    Aittokallio, Tero
    Cox, Rebecca J.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hukkanen, Veijo
    Marjomaki, Varpu
    Julkunen, Ilkka
    Vapalahti, Olli
    Tenson, Tanel
    Merits, Andres
    Kainov, Denis
    Novel activities of safe-in-human broad-spectrum antiviral agents2018Ingår i: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 154, s. 174-182Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-inhuman antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.

  • 31.
    Islam, Koushikul
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Carlsson, Marcus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Enquist, Per-Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Qian, Weixing
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Marttila, Marko
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Strand, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Structural Modifications and Biological Evaluations of Rift Valley Fever Virus Inhibitors Identified from Chemical Library Screening2022Ingår i: ACS Omega, E-ISSN 2470-1343, Vol. 7, nr 8, s. 6854-6868Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Rift Valley fever virus (RVFV) is an emerging high-priority pathogen endemic in Africa with pandemic potential. There is no specific treatment or approved antiviral drugs for the RVFV. We previously developed a cell-based high-throughput assay to screen small molecules targeting the RVFV and identified a potential effective antiviral compound (1-N-(2-(biphenyl-4-yloxy)ethyl)propane-1,3-diamine) as a lead compound. Here, we investigated how structural modifications of the lead compound affected the biological properties and the antiviral effect against the RVFV. We found that the length of the 2-(3-aminopropylamino)ethyl chain of the compound was important for the compound to retain its antiviral activity. The antiviral activity was similar when the 2-(3-aminopropylamino)ethyl chain was replaced with a butyl piperazine chain. However, we could improve the cytotoxicity profile of the lead compound by changing the phenyl piperazine linker from the para-position (compound 9a) to the meta-position (compound 13a). Results from time-of-addition studies suggested that compound 13a might be active during virus post-entry and/or the replication phase of the virus life cycle and seemed to affect the K+ channel. The modifications improved the properties of our lead compound, and our data suggest that 13a is a promising candidate to evaluate further as a therapeutic agent for RVFV infection.

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  • 32.
    Islam, Md. Koushikul
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Baudin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Eriksson, Jonas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Öberg, Christopher
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Habjan, Matthias
    Weber, Friedemann
    Överby, Anna K.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    High-Throughput Screening Using a Whole-Cell Virus Replication Reporter Gene Assay to Identify Inhibitory Compounds against Rift Valley Fever Virus Infection2016Ingår i: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 21, nr 4, s. 354-362Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rift Valley fever virus (RVFV) is an emerging virus that causes serious illness in humans and livestock. There are no approved vaccines or treatments for humans. The purpose of the study was to identify inhibitory compounds of RVFV infection without any preconceived idea of the mechanism of action. A whole-cell-based high-throughput drug screening assay was developed to screen 28,437 small chemical compounds targeting RVFV infection. To accomplish both speed and robustness, a replication-competent NSs-deleted RVFV expressing a fluorescent reporter gene was developed. Inhibition of fluorescence intensity was quantified by spectrophotometry and related to virus infection in human lung epithelial cells (A549). Cell toxicity was assessed by the Resazurin cell viability assay. After primary screening, 641 compounds were identified that inhibited RVFV infection by 80%, with 50% cell viability at 50 mu M concentration. These compounds were subjected to a second screening regarding dose-response profiles, and 63 compounds with 60% inhibition of RVFV infection at 3.12 mu M compound concentration and 50% cell viability at 25 mu M were considered hits. Of these, six compounds with high inhibitory activity were identified. In conclusion, the high-throughput assay could efficiently and safely identify several promising compounds that inhibited RVFV infection.

  • 33.
    Islam, Md. Koushikul
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Strand, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Saleeb, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Svensson, Richard
    Baranczewski, Pawel
    Artursson, Per
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Elofsson, Mikael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 1925Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rift Valley fever virus (RVFV) is a mosquito-borne hemorrhagic fever virus affecting both humans and animals with severe morbidity and mortality and is classified as a potential bioterror agent due to the possible aerosol transmission. At present there is no human vaccine or antiviral therapy available. Thus, there is a great need to develop new antivirals for treatment of RVFV infections. Benzavir-2 was previously identified as potent inhibitor of human adenovirus, herpes simplex virus type 1, and type 2. Here we assess the anti-RVFV activity of benzavir-2 together with four structural analogs and determine pre-clinical pharmacokinetic parameters of benzavir-2. In vitro, benzavir-2 efficiently inhibited RVFV infection, viral RNA production and production of progeny viruses. In vitro, benzavir-2 displayed satisfactory solubility, good permeability and metabolic stability. In mice, benzavir-2 displayed oral bioavailability with adequate maximum serum concentration. Oral administration of benzavir-2 formulated in peanut butter pellets gave high systemic exposure without any observed toxicity in mice. To summarize, our data demonstrated potent anti-RVFV activity of benzavir-2 in vitro together with a promising pre-clinical pharmacokinetic profile. This data support further exploration of the antiviral activity of benzavir-2 in in vivo efficacy models that may lead to further drug development for human use.

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  • 34. Khalil, Hussein
    et al.
    Ecke, Frauke
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Bucht, Göran
    Hörnfeldt, Birger
    Population Dynamics of Bank Voles Predicts Human Puumala Hantavirus Risk2019Ingår i: EcoHealth, ISSN 1612-9202, E-ISSN 1612-9210, Vol. 16, nr 3, s. 545-557Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Predicting risk of zoonotic diseases, i.e., diseases shared by humans and animals, is often complicated by the population ecology of wildlife host(s). We here demonstrate how ecological knowledge of a disease system can be used for early prediction of human risk using Puumala hantavirus (PUUV) in bank voles (Myodes glareolus), which causes Nephropathia epidemica (NE) in humans, as a model system. Bank vole populations at northern latitudes exhibit multiannual fluctuations in density and spatial distribution, a phenomenon that has been studied extensively. Nevertheless, existing studies predict NE incidence only a few months before an outbreak. We used a time series on cyclic bank vole population density (1972–2013), their PUUV infection rates (1979–1986; 2003–2013), and NE incidence in Sweden (1990–2013). Depending on the relationship between vole density and infection prevalence (proportion of infected animals), either overall density of bank voles or the density of infected bank voles may be used to predict seasonal NE incidence. The density and spatial distribution of voles at density minima of a population cycle contribute to the early warning of NE risk later at its cyclic peak. When bank voles remain relatively widespread in the landscape during cyclic minima, PUUV can spread from a high baseline during a cycle, culminating in high prevalence in bank voles and potentially high NE risk during peak densities.

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  • 35. Khalil, Hussein
    et al.
    Ecke, Frauke
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hornfeldt, Birger
    Selective predation on hantavirus-infected voles by owls and confounding effects from landscape properties2016Ingår i: Oecologia, ISSN 0029-8549, E-ISSN 1432-1939, Vol. 181, nr 2, s. 597-606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It has been suggested that predators may protect human health through reducing disease-host densities or selectively preying on infected individuals from the population. However, this has not been tested empirically. We hypothesized that Tengmalm's owl (Aegolius funereus) selectively preys on hantavirus-infected individuals of its staple prey, the bank vole (Myodes glareolus). Bank voles are hosts of Puumala hantavirus, which causes a form of hemorrhagic fever in humans. Selective predation by owls on infected voles may reduce human disease risk. We compared the prevalence of anti-Puumala hantavirus antibodies (seroprevalence), in bank voles cached by owls in nest boxes to seroprevalence in voles trapped in closed-canopy forest around each nest box. We found no general difference in seroprevalence. Forest landscape structure could partly account for the observed patterns in seroprevalence. Only in more connected forest patches was seroprevalence in bank voles cached in nest boxes higher than seroprevalence in trapped voles. This effect disappeared with increasing forest patch isolation, as seroprevalence in trapped voles increased with forest patch isolation, but did not in cached voles. Our results suggest a complex relationship between zoonotic disease prevalence in hosts, their predators, and landscape structure. Some mechanisms that may have caused the seroprevalence patterns in our results include higher bank vole density in isolated forest patches. This study offers future research potential to shed further light on the contribution of predators and landscape properties to human health.

  • 36. Khalil, Hussein
    et al.
    Ecke, Frauke
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Magnusson, Magnus
    Hornfeldt, Birger
    Declining ecosystem health and the dilution effect2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 31314Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The "dilution effect" implies that where species vary in susceptibility to infection by a pathogen, higher diversity often leads to lower infection prevalence in hosts. For directly transmitted pathogens, non-host species may "dilute" infection directly (1) and indirectly (2). Competitors and predators may (1) alter host behavior to reduce pathogen transmission or (2) reduce host density. In a well-studied system, we tested the dilution of the zoonotic Puumala hantavirus (PUUV) in bank voles (Myodes glareolus) by two competitors and a predator. Our study was based on long-term PUUV infection data (2003-2013) in northern Sweden. The field vole (Microtus agrestis) and the common shrew (Sorex araneus) are bank vole competitors and Tengmalm's owl (Aegolius funereus) is a main predator of bank voles. Infection probability in bank voles decreased when common shrew density increased, suggesting that common shrews reduced PUUV transmission. Field voles suppressed bank vole density in meadows and clear-cuts and indirectly diluted PUUV infection. Further, Tengmalm's owl decline in 1980-2013 may have contributed to higher PUUV infection rates in bank voles in 2003-2013 compared to 1979-1986. Our study provides further evidence for dilution effect and suggests that owls may have an important role in reducing disease risk.

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  • 37. Khalil, Hussein
    et al.
    Hörnfeldt, Birger
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Magnusson, Magnus
    Olsson, Gert
    Ecke, Frauke
    Dynamics and Drivers of Hantavirus Prevalence in Rodent Populations2014Ingår i: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 14, nr 8, s. 537-551Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Human encroachment on wildlife habitats has contributed to the emergence of several zoonoses. Pathogenic hantaviruses are hosted by rodents and cause severe diseases in the Americas and Eurasia. We reviewed several factors that potentially drive prevalence (the proportion of infected rodents) in host populations. These include demography, behavior, host density, small mammal diversity, predation, and habitat and landscape characteristics. This review is the first to include a quantitative summary of the literature investigating hantavirus prevalence in rodents. Demographic structure and density were investigated the most and predation the least. Reported effects of demographic structure and small mammal diversity were consistent, whereby reproductive males were most likely to be infected and prevalence decreased with small mammal diversity. The influences of habitat and landscape properties are often complex and indirect. The relationship between density and prevalence merits more investigation. Most hantavirus hosts are habitat generalists and their control is challenging. Incorporating all potential factors and their interactions is essential to understanding and controlling infection in host populations.

  • 38. Khalil, Hussein
    et al.
    Olsson, Gert
    Ecke, Frauke
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hjertqvist, Marika
    Magnusson, Magnus
    Löfvenius, Mikaell Ottosson
    Hörnfeldt, Birger
    The importance of bank vole density and rainy winters in predicting nephropathia epidemica incidence in Northern Sweden.2014Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 11, artikel-id e111663Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pathogenic hantaviruses (family Bunyaviridae, genus Hantavirus) are rodent-borne viruses causing hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In Europe, there are more than 10,000 yearly cases of nephropathia epidemica (NE), a mild form of HFRS caused by Puumala virus (PUUV). The common and widely distributed bank vole (Myodes glareolus) is the host of PUUV. In this study, we aim to explain and predict NE incidence in boreal Sweden using bank vole densities. We tested whether the number of rainy days in winter contributed to variation in NE incidence. We forecast NE incidence in July 2013-June 2014 using projected autumn vole density, and then considering two climatic scenarios: 1) rain-free winter and 2) winter with many rainy days. Autumn vole density was a strong explanatory variable of NE incidence in boreal Sweden in 1990-2012 (R2 = 79%, p<0.001). Adding the number of rainy winter days improved the model (R2 = 84%, p<0.05). We report for the first time that risk of NE is higher in winters with many rainy days. Rain on snow and ground icing may block vole access to subnivean space. Seeking refuge from adverse conditions and shelter from predators, voles may infest buildings, increasing infection risk. In a rainy winter scenario, we predicted 812 NE cases in boreal Sweden, triple the number of cases predicted in a rain-free winter in 2013/2014. Our model enables identification of high risk years when preparedness in the public health sector is crucial, as a rainy winter would accentuate risk.

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  • 39. Khalil, Hussein
    et al.
    Olsson, Gert
    Magnusson, Magnus
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hornfeldt, Birger
    Ecke, Frauke
    Spatial prediction and validation of zoonotic hazard through micro-habitat properties: where does Puumala hantavirus hole - up?2017Ingår i: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 17, artikel-id 523Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To predict the risk of infectious diseases originating in wildlife, it is important to identify habitats that allow the co-occurrence of pathogens and their hosts. Puumala hantavirus (PUUV) is a directly-transmitted RNA virus that causes hemorrhagic fever in humans, and is carried and transmitted by the bank vole (Myodes glareolus). In northern Sweden, bank voles undergo 3-4 year population cycles, during which their spatial distribution varies greatly.

    Methods: We used boosted regression trees; a technique inspired by machine learning, on a 10 - year time-series (fall 2003-2013) to develop a spatial predictive model assessing seasonal PUUV hazard using micro-habitat variables in a landscape heavily modified by forestry. We validated the models in an independent study area approx. 200 km away by predicting seasonal presence of infected bank voles in a five-year-period (2007-2010 and 2015).

    Results: The distribution of PUUV-infected voles varied seasonally and inter-annually. In spring, micro-habitat variables related to cover and food availability in forests predicted both bank vole and infected bank vole presence. In fall, the presence of PUUV-infected voles was generally restricted to spruce forests where cover was abundant, despite the broad landscape distribution of bank voles in general. We hypothesize that the discrepancy in distribution between infected and uninfected hosts in fall, was related to higher survival of PUUV and/ or PUUV-infected voles in the environment, especially where cover is plentiful.

    Conclusions: Moist and mesic old spruce forests, with abundant cover such as large holes and bilberry shrubs, also providing food, were most likely to harbor infected bank voles. The models developed using long-term and spatially extensive data can be extrapolated to other areas in northern Fennoscandia. To predict the hazard of directly transmitted zoonoses in areas with unknown risk status, models based on micro-habitat variables and developed through machine learning techniques in well-studied systems, could be used.

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  • 40. Kirui, Jared
    et al.
    Abidine, Yara
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Lenman, Annasara
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Centre for Experimental and Clinical Infection Research, TWINCORE, Institute for Experimental Virology, a Joint Venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany.
    Islam, Md. Koushikul
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Yong-Dae, Gwon
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Lasswitz, Lisa
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Bally, Marta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Gerold, Gisa
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Centre for Experimental and Clinical Infection Research, TWINCORE, Institute for Experimental Virology, a Joint Venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.
    The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry2021Ingår i: Cells, E-ISSN 2073-4409, Vol. 10, nr 7, artikel-id 1828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced cell binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.

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  • 41. Lindgren, Therese
    et al.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Mohamed, Nahla
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ljunggren, Hans-Gustaf
    Björkström, Niklas K
    Longitudinal analysis of the human T cell response during acute hantavirus infection2011Ingår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 85, nr 19, s. 10252-10260Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Longitudinal studies of T cell immune responses during viral infections in humans are essential for our understanding of how effector T cell responses develop, clear infection, and provide long-lasting immunity. Here, following an outbreak of a Puumala hantavirus infection in the human population, we longitudinally analyzed the primary CD8 T cell response in infected individuals from the first onset of clinical symptoms until viral clearance. A vigorous CD8 T cell response was observed early following the onset of clinical symptoms, determined by the presence of high numbers of Ki67(+)CD38(+)HLA-DR(+) effector CD8 T cells. This response encompassed up to 50% of total blood CD8 T cells, and it subsequently contracted in parallel with a decrease in viral load. Expression levels of perforin and granzyme B were high throughout the initial T cell response and likewise normalized following viral clearance. When monitoring regulatory components, no induction of regulatory CD4 or CD8 T cells was observed in the patients during the infection. However, CD8 as well as CD4 T cells exhibited a distinct expression profile of inhibitory PD-1 and CTLA-4 molecules. The present results provide insight into the development of the T cell response in humans, from the very onset of clinical symptoms following a viral infection to resolution of the disease.

  • 42. Luande, Verah Nafula
    et al.
    Eklöf, Disa
    Lindström, Anders
    Nyanjom, Steven Ger
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Lilja, Tobias
    The Human Biting Culex pipiens Bioform molestus Detected in Several Areas in Southern Sweden2020Ingår i: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 20, nr 12, s. 936-938Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The mosquito species Culex pipiens is a known vector of several pathogens and occurs in two distinct bioforms, pipiens and molestus. The bioform molestus thrives in urban environments where there are below-ground habitats; it can mate in confined spaces and feed on mammals as well as birds. In contrast, the bioform pipiens is found above ground, is thought to require more space for mating, and mainly feeds on birds. The pipiens bioform is present in large parts of Sweden but the molestus bioform has previously only been found in major cities.

    Materials and Methods: People experiencing mosquito nuisance in southern Sweden submitted mosquito samples as part of a citizen science project, and these samples were analyzed to determine the geographical distribution of the molestus bioform of Cx. pipiens. Mosquito specimens were identified to the species level by DNA barcoding of the cytochrome C oxidase subunit I (COI) gene, and the bioforms were determined through the CQ11 microsatellite marker.

    Results:Culex pipiens f molestus was observed to be spread across large parts of Gothenburg as well as in the suburbs. This bioform was found both in urban and rural areas at several sites across southern Sweden. In one site, hybrids between the two bioforms were found.

    Conclusions: The detection of Cx. pipiens f molestus in several rural areas was surprising, indicating that it may be more widely spread than urban areas alone, where it has been previously reported.

  • 43. Lundström, Jan O
    et al.
    Schäfer, Martina L
    Hesson, Jenny C
    Blomgren, Eric
    Lindström, Anders
    Wahlqvist, Pernilla
    Halling, Arne
    Hagelin, Anna
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Broman, Tina
    CBNR Defense and Security, Swedish Defense Research Agency, SE-90185 Umeå, Sweden.
    Forsman, Mats
    CBNR Defense and Security, Swedish Defense Research Agency, SE-90185 Umeå, Sweden.
    Persson Vinnersten, Thomas Z
    The geographic distribution of mosquito species in Sweden2013Ingår i: Journal of the European Mosquito Control Association, Vol. 31, s. 21-35Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Surveillance of the actual distribution of mosquito species in Northern Europe is fundamental for evaluating risk for emerging pathogens, and for research on potential vectors. The Swedish mosquito fauna composition and geographic distribution, originally described by Professor Christine Dahl in the 1970´s, included 43 species. We have compiled the information published from 1978 to 2012, and our own surveillance data from 2001 to 2013, and compared this with the species list and geographic distribution provided in "Taxonomy and geographic distribution of Swedish Culicidae" by Dahl (1977). New species detected during these 36 years were Culiseta (Culicella) ochroptera (Peus, 1935) published 1984, Aedes (Aedes) rossicus Dolbeskin, Goritzkaja & Mitrofanova, 1930 published 1986, Anopheles (Anopheles) beklemishevi published 1986, Aedes (Ochlerotatus) euedes (Howard, Dyar & Knab, 1912) published 2001, Aedes (Ochlerotatus) nigrinus (Eckstein, 1918) first recorded in 2012, and Anopheles (Anopheles) algeriensis Theobald, 1903, first recorded in 2013. We provide maps with the distribution by province for each species, including historic information up until 1977, and new records from 1978 to 2013, showing the similarities and differences between the old and the new records. Important findings in recent years include the wide distribution of the Sindbis virus enzootic vector Culex (Culex) torrentium Martinii, 1925, and the more limited distribution of the potential West Nile virus vector Culex (Culex) pipiens Linnaeus, 1758. The updated list of mosquito species in Sweden now includes 49 species.

  • 44.
    Lwande, Olivia Wesula
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Bucht, Goran
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Ahlm, Kristoffer
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Naslund, Jonas
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Mosquito-borne Inkoo virus in northern Sweden - isolation and whole genome sequencing2017Ingår i: Virology Journal, E-ISSN 1743-422X, Vol. 14, artikel-id 61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Inkoo virus (INKV) is a less known mosquito-borne virus belonging to Bunyaviridae, genus Orthobunyavirus, California serogroup. Studies indicate that INKV infection is mainly asymptomatic, but can cause mild encephalitis in humans. In northern Europe, the sero-prevalence against INKV is high, 41% in Sweden and 51% in Finland. Previously, INKV RNA has been detected in adult Aedes (Ae.) communis, Ae. hexodontus and Ae. punctor mosquitoes and Ae. communis larvae, but there are still gaps of knowledge regarding mosquito vectors and genetic diversity. Therefore, we aimed to determine the occurrence of INKV in its mosquito vector and characterize the isolates.

    Methods: About 125,000 mosquitoes were collected during a mosquito-borne virus surveillance in northern Sweden during the summer period of 2015. Of these, 10,000 mosquitoes were processed for virus isolation and detection using cell culture and RT-PCR. Virus isolates were further characterized by whole genome sequencing. Genetic typing of mosquito species was conducted by cytochrome oxidase subunit I (COI) gene amplification and sequencing (genetic barcoding).

    Results: Several Ae. communis mosquitoes were found positive for INKV RNA and two isolates were obtained. The first complete sequences of the small (S), medium (M), and large (L) segments of INKV in Sweden were obtained. Phylogenetic analysis showed that the INKV genome was most closely related to other INKV isolates from Sweden and Finland. Of the three INKV genome segments, the INKV M segment had the highest frequency of non-synonymous mutations. The overall G/C-content of INKV genes was low for the N/NSs genes (43.8–45.5%), polyprotein (Gn/Gc/NSm) gene (35.6%) and the RNA polymerase gene (33.8%) This may be due to the fact that INKV in most instances utilized A or T in the third codon position.

    Conclusions: INKV is frequently circulating in northern Sweden and Ae. communis is the key vector. The high mutation rate of the INKV M segment may have consequences on virulence

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  • 45.
    Lwande, Olivia Wesula
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Luande, Verah Nafula
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Pereira de Freitas, Amanda
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Tajedin, Leila
    Department of Microsystems, University of South-Eastern Norway, Vestfold, Norway.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Näslund, Jonas
    Swedish Defence Research Agency, CBRN, Defence and Security, Umeå, Sweden.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Bucht, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Europeiska CBRNE-centret.
    Mismatch amplification mutation assays of Chikungunya virus and O'Nyong-Nyong virus: a simple and reliable method for surveillance and identification of emerging alphaviruses2022Ingår i: Frontiers in Virology, ISSN 2673-818X, Vol. 2, artikel-id 769354Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The mosquito-borne alphaviruses chikungunya virus (CHIKV) and o'nyong-nyong virus (ONNV) are closely related Alphaviruses that belong to the Semliki forest virus serocomplex. The two viruses are associated with large outbreaks with significant morbidity. However, they are transmitted by different mosquito vectors and accordingly need different prevention strategies. The viruses are difficult to distinguish clinically and there is a lack of sensitive and specific assays that can discriminate between CHIKV and ONNV. Therefore, there is a need for new methods that may be able to determine the true burden of the diseases caused by these viruses, especially in resource-poor settings.

    Method: To distinguish between CHIKV and ONNV, we designed and optimized two genetic methods, melt analysis of mismatch amplification mutation assay (Melt-MAMA) and agarose gel-based mismatch amplification mutation assay (Agarose-MAMA). The identification was based on single nucleotide polymorphisms using two competing forward primers and a common reverse primer that targeted selected sites in the envelope genes (E1 and E2). A specific shift in the melting point and mobility on agarose gels was obtained by tailing one of the two competing primers with a G/C-rich stretch of nucleotides.

    Results: The melting point analyses by real-time polymerase chain reaction (qPCR Melt-MAMA) or gel-shift assay (Agarose-MAMA assay) for CHIKV and ONNV were found to be reproducible and the sensitivity of the two assays was estimated at under 100 template copies/reaction. Furthermore, no cross-reactivity with related viruses of the same serocomplex such as Mayaro virus, Ross River virus or Semliki forest virus was detected, or with other viruses such as Sindbis virus (Alphavirus), West Nile virus, dengue virus (Flavivirus), Inkoo virus and Tahyna virus (Orthobunyavirus). The results from the two assays were comparable when the obtained amplicons were analyzed by Melt-MAMA or by Agarose-MAMA.

    Conclusion: Herein we present reliable and robust methods that can discriminate between CHIKV and ONNV. These methods can be used in well-equipped laboratories and basic clinical settings (e.g., in developing countries), as well as in field situations. The approach may also be applicable in the distinction of other closely-related mosquito-borne viruses that belong to the same serogroup.

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  • 46.
    Lwande, Olivia Wesula
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Mohamed, Nahla
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Bucht, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Olsson, Gert
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Seewis hantavirus in common shrew (Sorex araneus) in Sweden2020Ingår i: Virology Journal, E-ISSN 1743-422X, Vol. 17, nr 1, artikel-id 198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Rodent borne hantaviruses are emerging viruses infecting humans through inhalation. They cause hemorrhagic fever with renal syndrome and hemorrhagic cardiopulmonary syndrome. Recently, hantaviruses have been detected in other small mammals such as Soricomorpha (shrews, moles) and Chiroptera (bats), suggested as reservoirs for potential pandemic viruses and to play a role in the evolution of hantaviruses. It is important to study the global virome in different reservoirs, therefore our aim was to investigate whether shrews in Sweden carried any hantaviruses. Moreover, to accurately determine the host species, we developed a molecular method for identification of shrews.

    Method: Shrews (n = 198), caught during 1998 in Sweden, were screened with a pan-hantavirus PCR using primers from a conserved region of the large genome segment. In addition to morphological typing of shrews, we developed a molecular based typing method using sequencing of the mitochondrial cytochrome C oxidase I (COI) and cytochrome B (CytB) genes. PCR amplified hantavirus and shrew fragments were sequenced and phylogenetically analysed.

    Results: Hantavirus RNA was detected in three shrews. Sequencing identified the virus as Seewis hantavirus (SWSV), most closely related to previous isolates from Finland and Russia. All three SWSV sequences were retrieved from common shrews (Sorex araneus) sampled in Västerbotten County, Sweden. The genetic assay for shrew identification was able to identify native Swedish shrew species, and the genetic typing of the Swedish common shrews revealed that they were most similar to common shrews from Russia.

    Conclusion: We detected SWSV RNA in Swedish common shrew samples and developed a genetic assay for shrew identification based on the COI and CytB genes. This was the first report of presence of hantavirus in Swedish shrews.

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  • 47.
    Lwande, Olivia Wesula
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Näslund, Jonas
    Lundmark, Eva
    Ahlm, Kristoffer
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Ahlm, Clas
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Bucht, Göran
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Experimental Infection and Transmission Competence of Sindbis Virus in Culex torrentium and Culex pipiens Mosquitoes from Northern Sweden2019Ingår i: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 19, nr 2, s. 128-133Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Sindbis virus (SINV) is a mosquito-borne Alphavirus known to infect birds and cause intermittent outbreaks among humans in Fenno-Scandia. In Sweden, the endemic area has mainly been in central Sweden. Recently, SINV infections have emerged to northern Sweden, but the vectorial efficiency for SINV of mosquito species in this northern region has not yet been ascertained.

    Objective: Mosquito larvae were sampled from the Umea region in northern Sweden and propagated in a laboratory to adult stage to investigate the infection, dissemination, and transmission efficiency of SINV in mosquitoes.

    Materials and Methods: The mosquito species were identified by DNA barcoding of the cytochrome oxidase I gene. Culex torrentium was the most abundant (82.2%) followed by Culex pipiens (14.4%), Aedes annulipes (1.1%), Anopheles claviger (1.1%), Culiseta bergrothi (1.1%), or other unidentified species (1.1%). Mosquitoes were fed with SINV-infected blood and monitored for 29 days to determine the viral extrinsic incubation period. Infection and dissemination were determined by RT-qPCR screening of dissected body parts of individual mosquitoes. Viral transmission was determined from saliva collected from individual mosquitoes at 7, 14, and 29 days. SINV was detected by cell culture using BHK-21 cells, RT-qPCR, and sequencing.

    Results: Cx. torrentium was the only mosquito species in our study that was able to transmit SINV. The overall transmission efficiency of SINV in Cx. torrentium was 6.8%. The rates of SINV infection, dissemination, and transmission in Cx. torrentium were 11%, 75%, and 83%, respectively.

    Conclusions: Cx. torrentium may be the key vector involved in SINV transmission in northern Sweden.

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  • 48.
    Lwande, Olivia Wesula
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Näslund, Jonas
    Swedish Defence Research Agency, CBRN, Defence and Security, Umeå, Sweden.
    Sjödin, Andreas
    Swedish Defence Research Agency, CBRN, Defence and Security, Umeå, Sweden.
    Lantto, Rebecca
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Luande, Verah Nafula
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Bucht, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Agwanda, Bernard
    Mammalogy Section, National Museums of Kenya, Nairobi, Kenya.
    Obanda, Vincent
    Department of Research Permitting and Compliance Wildlife Research and Training Institute, Naivasha, Kenya.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Novel strains of Culex flavivirus and Hubei chryso-like virus 1 from the Anopheles mosquito in western Kenya2024Ingår i: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 339, artikel-id 199266Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Surveillance of mosquito vectors is critical for early detection, prevention and control of vector borne diseases. In this study we used advanced molecular tools, such as DNA barcoding in combination with novel sequencing technologies to discover new and already known viruses in genetically identified mosquito species. Mosquitoes were captured using BG sentinel traps in Western Kenya during May and July 2019, and homogenized individually before pooled into groups of ten mosquitoes. The pools and individual samples were then used for molecular analysis and to infect cell cultures. Of a total of fifty-four (54) 10-pools, thirteen (13) showed cytopathic effect (CPE) on VeroB4 cells, eighteen (18) showed CPE on C6/36 cells. Eight (8) 10-pools out of the 31 CPE positive pools showed CPE on both VeroB4 and C6/36 cells. When using reverse transcriptase polymerase chain reaction (RT-PCR), Sanger sequencing and Twist Comprehensive Viral Research Panel (CVRP) (Twist Biosciences), all pools were found negative by RT-PCR when using genus specific primers targeting alphaviruses, orthobunyaviruses and virus specific primers towards o'nyong-nyong virus, chikungunya virus and Sindbis virus (previously reported to circulate in the region). Interestingly, five pools were RT-PCR positive for flavivirus. Two of the RT-PCR positive pools showed CPE on both VeroB4 and C6/36 cells, two pools showed CPE on C6/36 cells alone and one pool on VeroB4 cells only. Fifty individual mosquito homogenates from the five RT-PCR positive 10-pools were analyzed further for flavivirus RNA. Of these, 19 out of the 50 individual mosquito homogenates indicated the presence of flavivirus RNA. Barcoding of the flavivirus positive mosquitoes revealed the mosquito species as Aedes aegypti (1), Mansonia uniformis (6), Anopheles spp (3), Culex pipiens (5), Culex spp (1), Coquilletidia metallica (2) and Culex quinquefasciatus (1). Of the 19 flavivirus positive individual mosquitoes, five (5) virus positive homogenates were sequenced. Genome sequences of two viruses were completed. One was identified as the single-stranded RNA Culex flavivirus and the other as the double-stranded RNA Hubei chryso-like virus 1. Both viruses were found in the same Anopheles spp. homogenate extracted from a sample that showed CPE on both VeroB4 and C6/36 cells. The detection of both viruses in a single mosquito homogenate indicated coinfection. Phylogenetic analyses suggested that the Culex flavivirus sequence detected was closely related to a Culex flavivirus isolated from Uganda in 2008. All four Hubei chryso-like virus 1 segments clusters closely to Hubei chryso-like virus 1 strains isolated in Australia, China and USA. Two novel strains of insect-specific viruses in Anopheles mosquitoes were detected and characterized.

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  • 49.
    Lwande, Olivia Wesula
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Obanda, Vincent
    Veterinary Services Department, Kenya Wildlife Service, Nairobi, Kenya.
    Bucht, Göran
    Swedish Defence Research Agency, CBRN Defence and Security, Umeå, Sweden.
    Mosomtai, Gladys
    Earth Observation Unit, International Centre of Insect Physiology and Ecology, Nairobi, Kenya.
    Otieno, Viola
    IGAD Climate Prediction and Application Centre (ICPAC), Nairobi, Kenya.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Global emergence of Alphaviruses that cause arthritis in humans2015Ingår i: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 5, nr 1, artikel-id 29853Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Arthropod-borne viruses (arboviruses) may cause severe emerging and re-emerging infectious diseases, which pose a significant threat to human and animal health in the world today. These infectious diseases range from mild febrile illnesses, arthritis, and encephalitis to haemorrhagic fevers. It is postulated that certain environmental factors, vector competence, and host susceptibility have a major impact on the ecology of arboviral diseases. Presently, there is a great interest in the emergence of Alphaviruses because these viruses, including Chikungunya virus, O'nyong'nyong virus, Sindbis virus, Ross River virus, and Mayaro virus, have caused outbreaks in Africa, Asia, Australia, Europe, and America. Some of these viruses are more common in the tropics, whereas others are also found in temperate regions, but the actual factors driving Alphavirus emergence and re-emergence remain unresolved. Furthermore, little is known about the transmission dynamics, pathophysiology, genetic diversity, and evolution of circulating viral strains. In addition, the clinical presentation of Alphaviruses may be similar to other diseases such as dengue, malaria, and typhoid, hence leading to misdiagnosis. However, the typical presence of arthritis may distinguish between Alphaviruses and other differential diagnoses. The absence of validated diagnostic kits for Alphaviruses makes even routine surveillance less feasible. For that purpose, this review describes the occurrence, genetic diversity, clinical characteristics, and the mechanisms involving Alphaviruses causing arthritis in humans. This information may serve as a basis for better awareness and detection of Alphavirus-caused diseases during outbreaks and in establishing appropriate prevention and control measures.

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  • 50.
    Lwande, Olivia Wesula
    et al.
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Obanda, Vincent
    Lindstrom, Anders
    Ahlm, Clas
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Evander, Magnus
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Näslund, Jonas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Europeiska CBRNE-centret.
    Bucht, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Europeiska CBRNE-centret.
    Globe-Trotting Aedes aegypti and Aedes albopictus: Risk Factors for Arbovirus Pandemics2020Ingår i: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 20, nr 2, s. 71-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Two species of Aedes (Ae.) mosquitoes (Ae. aegypti and Ae. albopictus) are primary vectors for emerging arboviruses that are a significant threat to public health and economic burden worldwide. Distribution of these vectors and the associated arboviruses, such as dengue virus, chikungunya virus, yellow fever virus, and Zika virus, was for a long time restricted by geographical, ecological, and biological factors. Presently, arbovirus emergence and dispersion are more rapid and geographically widespread, largely due to expansion of the range for these two mosquitoes that have exploited the global transportation network, land perturbation, and failure to contain the mosquito population coupled with enhanced vector competence. Ae. aegypti and Ae. albopictus may also sustain transmission between humans without having to depend on their natural reservoir forest cycles due to arthropod adaptation to urbanization. Currently, there is no single strategy that is adequate to control these vectors, especially when managing arbovirus outbreaks. Objective: This review aimed at presenting the characteristics and abilities of Ae. aegypti and Ae. albopictus, which can drive a global public health risk, and suggests strategies for prevention and control. Methods: This review presents the geographic range, reproduction and ecology, vector competence, genetic evolution, and biological and chemical control of these two mosquito species and how they have changed and developed over time combined with factors that may drive pandemics and mitigation measures. Conclusion: We suggest that more efforts should be geared toward the development of a concerted multidisciplinary approach.

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