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  • 1. Affognon, H.
    et al.
    Mburu, P.
    Hassan, Osama Ahmed
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Kingori, S.
    Ahlm, C.
    Sang, R.
    Evander, M.
    Sociocultural differences affect Rift Valley fever exposureManuskript (preprint) (Annet vitenskapelig)
  • 2. 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 Kenya2017Inngår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, nr 3, e0005405Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 3.
    Ahlm, Clas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Alexeyev, O A
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Aava, Birgitta
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Tärnvik, Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Palo, T
    High prevalence of hantavirus antibodies in bank voles (Clethrionomys glareolus) captured in the vicinity of households afflicted with nephropathia epidemica.1997Inngår i: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, Vol. 56, nr 6, 674-8 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Puumala virus, the causative agent of nephropathia epidemica (NE), occurs endemically in Europe and is spread mainly by the bank vole (Clethrionomys glareolus). In the vicinity of each of four households afflicted with NE, we studied rodents with regard to population density and prevalence of Puumala virus-specific antibodies. For each case area, a control area was randomly selected 10 km away, without regard to the presence of human settlement. During 6,000 trap nights, 328 rodents were caught, of which 299 were C. glareolus. The mean rodent densities of case and control areas were 6.6 and 3.7 animals per 100 trap nights (P < 0.001). The prevalence of serum antibodies was 15.9% in case areas compared with 5.6% in control areas (P < 0.05). In three of the case areas, where NE had occurred 3-10 weeks before trapping, the rodent density and seroprevalence were much higher than in the fourth area, where NE occurred 38 weeks before trapping. In conclusion, C. glareolus seropositive for Puumala virus occurred more frequently near households afflicted with NE than in control areas 10 km away.

  • 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 Sweden2014Inngår i: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 142, nr 7, 1559-1565 s.Artikkel i tidsskrift (Fagfellevurdert)
    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).

  • 5.
    Ahlm, Clas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Stegmayr, Birgitta
    Settergren, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Tärnvik, Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Prevalence of serum antibodies to hantaviruses in northern Sweden as measured by recombinant nucleocapsid proteins.1997Inngår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 29, nr 4, 349-54 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An enzyme-linked immunosorbent assay (ELISA) based on recombinant nucleocapsid protein (rN delta) (aa 1-117) of Hantaan, Seoul, Dobrava, Sin Nombre and Puumala hantaviruses was used to determine the prevalence of antibodies among randomized and stratified individuals from northern Sweden. In total, 137/1533 individuals (8.9%) had specific serum IgG antibodies to Puumala virus, the only hantavirus known to occur in the region. The prevalence of antibodies to Puumala virus (8.9%) was determined to be higher than previously reported (5.4%) in the same serum material, by use of immunofluorescence assay. As expected, sera reactive to Puumala virus rN delta did frequently cross-react with Sin Nombre virus protein. Unexpectedly, 21/1533 (1.4%) individuals recognized the Sin Nombre virus rN delta exclusively. Another 8 subjects showed reactivity in the ELISA to Hantaan, Seoul, or Dobrava virus-derived rN delta but not Puumala virus or Sin Nombre virus rN delta. The present demonstration in some individuals of antibodies specifically recognizing the Sin Nombre, Dobrava, Hantaan and Seoul virus protein justifies an awareness of the possibility that hantaviruses antigenically different from Puumala virus might occur in the region.

  • 6.
    Ahlm, Clas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Linderholm, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Stegmayr, Birgitta
    Settergren, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Prevalence of serum IgG antibodies to Puumala virus (haemorrhagic fever with renal syndrome) in northern Sweden.1994Inngår i: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 113, nr 1, 129-36 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A stratified and randomly-selected population sample was identified in 1990 in order to study the seroprevalence of nephropathia epidemica (haemorrhagic fever with renal syndrome) in Northern Sweden. Sera from 1538 subjects (750 men, 788 women), 25-64 years of age, were analysed for the presence of Puumala virus (PUV) specific-IgG by the indirect immunofluorescence antibody test. Specific IgG was detected in sera from 83 subjects (5.4%). Men and women had similar seroprevalence rates. The highest seroprevalences were found in subjects 55 years or older (8.0%) and among farmers and forestry workers (15.9%). The geographic distribution of seropositive individuals was uneven and there were significantly more seropositive persons in rural than in urban areas (P < 0.05).

  • 7.
    Ahlm, Clas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Lindén, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Linderholm, M
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Alexeyev, O A
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Billheden, J
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Fagerlund, M
    Zetterlund, B
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurofysiologi.
    Settergren, B
    Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome)1998Inngår i: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 36, nr 2, 149-155 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Central nervous system (CNS) - related symptoms occur in haemorrhagic fever with renal syndrome (HFRS). To study the CNS and ophthalmic involvement in nephropathia epidemica (NE), the European type of HFRS, we included 26 patients in a prospective study. Most common CNS-related symptoms were headache (96%), insomnia (83%), vertigo (79%), nausea (79%), and vomiting (71%). Ophthalmic symptoms were reported by 82% of patients; 41% had photophobia and 50% had impaired vision. A transient loss of vision was recorded in one patient, who also had a generalized seizure. Minor white matter lesions were found in about half of the patients investigated with brain magnetic resonance imaging (MRI). Electroencephalography (EEG) showed severe alterations in only one patient, and slight and reversible patterns in another two patients. Neopterin, interleukin-6 and interferon-gamma levels in the cerebrospinal fluid (CSF) were elevated, which may indicate immune activation. However, we found no evidence of intrathecal NE virus replication. We conclude that CNS-related symptoms are common in NE, and transient ophthalmic involvement can be demonstrated in about half of the patients.

  • 8.
    Ahlm, Clas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Thelin, Anders
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Stiernström, E L
    Holmberg, S
    Tärnvik, Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Prevalence of antibodies specific to Puumala virus among farmers in Sweden1998Inngår i: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, Vol. 24, nr 2, 104-108 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Serological evidence confirmed that the exposure of humans to Puumala virus is firmly restricted to the northern and central parts of Sweden. In addition the evidence indicated that, in this region, farming is associated with an increased risk of contracting hantavirus infection.

  • 9.
    Ahlm, Clas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Wallin, Kjell
    Skoglig zooekologi, SLU, Umeå.
    Lundkvist, Åke
    Smittskyddsinstitutet.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Merza, Malik
    Virologi, SVA, Uppsala.
    Tärnvik, Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Serologic evidence of Puumala virus infection in wild moose in northern Sweden2000Inngår i: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, Vol. 62, nr 1, 106-111 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Puumala (PUU) virus is the causative agent of nephropathia epidemica, the Scandinavian form of hemorrhagic fever with renal syndrome. The infection is acquired by airborne transmission of PUU virus from its rodent reservoir, the bank vole. Besides serologic data indicating that the virus may spread also to heterologous rodents, there is little information on the susceptibility of wild living animals to PUU virus. We studied the occurrence of antibodies to PUU virus in serum samples from 427 wild-living moose, of which 260 originated from the PUU virus-endemic northern and central parts of Sweden and 167 originated from the southern, nonendemic part of Sweden. Samples from 5 animals showed reactivity in an ELISA for recombinant PUU virus nucleocapsid protein, an immunofluorescent assay, and a neutralization test. These 5 animals all originated from the PUU virus-endemic northern part of Sweden. In conclusion, 5 of 260 moose from the endemic region showed convincing serologic evidence of past PUU virus infection. The seroprevalence was low, suggesting that the moose is subjected to endstage infection rather than being part of an enzootic transmission cycle.

  • 10.
    Ahmed Hassan Ahmed, Osama
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Rift Valley fever: challenges and new insights for prevention and control using the “One Health” approach2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Rift Valley fever (RVF) is an emerging viral zoonosis that causes frequent outbreaks in east Africa and on the Arabian Peninsula. The likelihood of RVF global expansion due to climate change and human anthropogenic factors is an important issue. The causative agent, RVF virus, is an arbovirus that is transmitted by several mosquito species and is able to infect a wide range of livestock as well as people. The infection leads to mass abortions and death in livestock and a potentially deadly hemorrhagic fever in humans. RVF has severe socio-economic consequences such as animal trade bans between countries, disruption of food security, and economic disaster for farmers and pastoralists as well as for countries. Human behavior such as direct contact with infected animals or their fluids and exposure to mosquito bites increases the risk for contracting the disease.

    To better understand the challenges associated with RVF outbreaks and to explore prevention and control strategies, we used the One Health approach. The local community had to be involved to understand the interaction between the environment, animals, and humans. We focused on Sudan, Saudi Arabia, and Kenya. First, we systematically reviewed the literature and then we performed cross sectional community-based studies using a special One Health questionnaire. Climatic and remote sensing data were used in combination with statistics to develop a sub-region predictive model for RVF.

    For both Saudi Arabia and Sudan, the ecology and environment of the affected areas were similar. These areas included irrigation canals and excessive rains that provide an attractive habitat for mosquito vectors to multiply. The surveillance systems were unable to detect the virus in livestock before it spread to humans. Ideally, livestock should serve as sentinels to prevent loss of human lives, but the situation here was reversed. Differences between countries regarding further spread of RVF was mainly determined by better economic and infrastructure resources.

    In Sudan, there was a lack of knowledge and appropriate practices at the studied community regarding RVF disease symptoms and risk factors for both animals and humans. The community was hesitant in notifying the authorities about RVF suspicion in livestock due to the lack of a compensation system. The perceived role of the community in controlling RVF was fragmented, increasing the probability of RVF transmission and disease.

    In Kenya, our study found that better knowledge about RVF does not always translate to more appropriate practices that avoid exposure to the disease. However, the combination of good knowledge, attitudes, and practices may explain why certain communities were less affected. Strategies to combat RVF should consider socio-cultural and behavioral differences among communities. We also noticed that RVF outbreaks in Kenya occurred in regions with high livestock density exposed to heavy rains and wet soil fluxes, which could be measured by evapotranspiration and vegetation seasonality variables. We developed a RVF risk map on a sub-regional scale. Future outbreaks could be better managed if such relevant RVF variables are integrated into early warning systems.

    To confront RVF outbreaks, a policy is needed that better incorporates ecological factors and human interactions with livestock and environment that help the RVF pathogen spread. Early detection and notification of RVF is essential because a delay will threaten the core of International Health Regulations (IHR), which emphasizes the share of information during a transboundary disease outbreak to avoid unnecessary geographical expansion.

  • 11.
    Alexeyev, O A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Billheden, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Settergren, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Elevated levels of total and Puumala virus-specific immunoglobulin E in the Scandinavian type of hemorrhagic fever with renal syndrome.1994Inngår i: Clinical and diagnostic laboratory immunology, ISSN 1071-412X, Vol. 1, nr 3, 269-72 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In a previous study, it was reported that the total immunoglobulin E (IgE) level was increased in patients with hemorrhagic fever with renal syndrome (HFRS). The aim of the present study was to investigate whether specific IgE is synthesized during the course of the disease. For this purpose, an epsilon-capture enzyme-linked immunosorbent assay was developed. A total of 72 patients with HFRS caused by Puumala virus were studied. Three different control groups were included: 20 blood donors, 20 patients with other viral diseases (influenza A and B virus, acute Epstein-Barr virus, and acute cytomegalovirus infections), and 5 subjects with high levels of total IgE (median, 1,070 kU/liter; range, 773 to 5,740 kU/liter). The levels of total IgE were significantly higher during the acute phase of HFRS than those of blood donors (P < 0.01) and of patients with other viral diseases (P < 0.001). All patients developed a specific IgE response (median, 55 arbitrary units; range 24 to 123 arbitrary units) in the acute phase of the disease, whereas in the different control groups no specific IgE was detectable. Both total and specific IgE levels decreased during convalescence compared with those during the acute phase of HFRS (P < 0.001 and P < 0.001, respectively). In conclusion, we have shown that both total and specific IgE levels are increased in patients with HFRS compared with levels in patients with other viral diseases. The possible pathogenetic role of the specific IgE response in HFRS is discussed.

  • 12.
    Alexeyev, O A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Stigbrand, Torgny
    Settergren, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hantavirus antigen detection using human serum immunoglobulin M as the capturing antibody in an enzyme-linked immunosorbent assay.1996Inngår i: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, Vol. 54, nr 4, 367-71 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An enzyme-linked immunosorbent assay (ELISA) was developed to detect different hantavirus antigens in cell culture; i.e. Puumala (PUU), Hantaan (HTN), and Dobrava (DOB) viruses. The assay was based on binding human serum immunoglobulin M (IgM) antibodies to the solid phase by use of goat anti-IgM antibodies. The captured IgM antibodies were present in the acute phase serum from two patients: one infected in Sweden and the other in Bosnia. Antigens being bound to the solid phase by the human anti-PUU and anti-DOB/HTN IgM antibodies were detected by a broadly reacting polyclonal rabbit anti PUU-recombinant nucleocapsid protein antiserum. The IgM isotype was proven to be at least five times more efficient than IgG when used as the capturing antibody. The sensitivity of the PUU antigen ELISA was approximately 0.5 ng/ml, as measured by titration with a PUU recombinant nucleoprotein antigen. Cell-associated PUU antigen in tissue culture was seen after 48 hr by the PUU-ELISA and after 96 hr by immunofluorescent assay. When tested for capacity to discriminate between PUU, DOB, and HTN viruses, significant differences were found: the Swedish serum detected PUU antigen at high titers, whereas no reactivity was found against DOB and HTN; the Bosnian serum detected both DOB and HTN at high titers but had a low reactivity to PUU. The method was also tested for its usefulness in detecting PUU antigen in bank vole (clethrionomys glareolus) lungs. Of 59 animals captured from the surroundings of patients with nephropathia epidemica, three became positive with a high activity in the PUU-ELISA, but with low reactivity in the DOB/HTN-ELISA. It is concluded that a sensitive ELISA has been developed to detect different hantaviruses in cell culture and lungs of bank voles.

  • 13.
    Alexeyev, Oleg A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Aava, Birgitta
    Skoglig Zooekologi, SLU, Umeå.
    Palo, Thomas
    Skoglig Zooekologi, SLU, Umeå.
    Settergren, Bo
    Tärnvik, Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    A minority of seropositive wild bank voles (Clethrionomys glareolus) show evidence of current Puumala virus infection1998Inngår i: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 121, nr 2, 419-425 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bank voles (Clethrionomys glareolus) serve as the reservoir for Puumala (PUU) virus, the aetiologic agent of nephropathia epidemica. The animals are believed to be persistently infected and the occurrence of serum antibodies is usually taken as an evidence of active infection. We found serum antibodies to PUU virus in 42 of 299 wild bank voles captured in a PUU virus endemic area. PUU virus RNA was demonstrated in lung specimens of 11 of these 42 animals and in 2 of them antigen was also found. Thus in the lungs of 31 of 42 seropositive animals neither PUU virus RNA nor antigen was detected. In 2 of 257 seronegative animals, lung specimens showed presence of PUU virus antigen and RNA. Isolation of PUU virus from lung tissue was successful in all 4 antigen-positive bank voles but in none of 16 tested antigen-negative animals. In conclusion, only a minority of bank voles with serum antibodies to PUU virus showed evidence of current infection.

  • 14.
    Alexeyev, Oleg A
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Marklund, Ingrid
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Virologi.
    Shannon, Beverley
    Golovleva, Irina
    Olsson, Jan
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Andersson, Charlotte
    Eriksson, Irene
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Virologi.
    Cohen, Ronald
    Elgh, Fredrik
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Virologi. Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Direct visualization of Propionibacterium acnes in prostate tissue by multicolor fluorescent in situ hybridization assay.2007Inngår i: Journal of Clinical Microbiology, ISSN 0095-1137, Vol. 45, nr 11, 3721-8 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Prostate tissues from patients with prostate cancer and benign prostatic hyperplasia (BPH) frequently contain histological inflammation, and a proportion of these patients show evidence of Propionibacterium acnes infection in the prostate gland. We developed a multicolor fluorescent in situ hybridization (FISH) assay targeting P. acnes 23S rRNA along with a 14-kb region of the P. acnes genome. This assay was used to analyze prostate tissues from patients with prostate cancer and BPH. P. acnes infection of the prostate gland was demonstrated in prostatic tissue in 5 of 10 randomly selected prostate cancer patients. FISH analysis and confocal laser microscopy imaging revealed intracellular localization and stromal biofilm-like aggregates as common forms of P. acnes infection in prostate tissues from both prostate cancer and BPH patients. A sequential analysis of prostate tissue from individual patients suggested that P. acnes can persist for up to 6 years in the prostate gland. These results indicate that P. acnes can establish a persistent infection in the prostate gland. Further study is needed to clarify the link between this bacterium and prostatic inflammation which may contribute to the development of BPH and prostate cancer.

  • 15.
    Alexeyev, Oleg
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Bergh, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Marklund, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Thellenberg Karlsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wiklund, Fredrik
    Grönberg, Henrik
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Association between the presence of bacterial 16S RNA in prostate specimens taken during transurethral resection of prostate and subsequent risk of prostate cancer (Sweden)2006Inngår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 17, nr 9, 1127-1133 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To study bacterial 16S RNA in archival prostate samples from 352 patients with benign prostate hyperplasia (BPH) and evaluate whether the presence of bacterial DNA was different in those who later developed prostate cancer (n = 171) and in the matched controls that did not progress to cancer (n = 181).

    Methods: 16S DNA PCR followed by cloning and sequencing the positive samples.

    Results: In 96/352 (27%) of the prostate tissue specimens 16S RNA were detected. Sequence analysis revealed Propionibacterium acnes as the predominant microorganism (23% of 16S RNA positive patients). The second most frequent isolate—Escherichia coli was found in 12 (12%) patients. The other isolates included Pseudomonas sp. (3 patients), Actinomyces sp. (2), Streptococcus mutans (1), Corynebacterium sp. (2),Nocardioides sp. (1), Rhodococcus sp. (1) Veillonella sp. (2). In P. acnes positive samples 62% exhibited severe histological inflammation versus 50% in the bacteria-negative group (p = 0.602). The presence of P. acnes in the prostate was associated with prostate cancer development (OR 2.17, 95% CI 0.77–6.95).

    Conclusions: This study has revealed P. acnes as the most common bacteria in the prostate in BPH. Further studies are needed to clarify its role in contributing to the development of prostatic inflammation and prostate cancer.

  • 16.
    Alexeyev, Oleg
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Olsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Is there evidence for a role of Propionibacterium acnes in prostatic disease?2009Inngår i: Urology, ISSN 1527-9995, Vol. 73, nr 2, 220-224 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 17.
    Allard, A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Albinsson, B
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Wadell, G
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Rapid typing of human adenoviruses by a general PCR combined with restriction endonuclease analysis.2001Inngår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 39, nr 2, 498-505 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have developed a system for rapid typing of adenoviruses (Ads) based on a combination of PCR and restriction endonuclease (RE) digestion (PCR-RE digestion). Degenerated consensus primers were designed, allowing amplification of DNA from all 51 human Ad prototype strains and altogether 44 different genome variants of Ad serotypes 1, 3, 4, 5, 7, 11, 19, 40, and 41. The 301-bp amplimer of 22 prototype strains representing all six subgenera and the genome variant was selected as a target for sequencing to look for subgenus and genome type variabilities. The sequences obtained were used to facilitate the selection of specific REs for discrimination purposes in a diagnostic assay by following the concept of cleavage or noncleavage of the 301-bp amplimer. On the basis of these results, a flowchart was constructed, allowing identification of subgenus B:2 and D serotypes and almost complete distinction of subgenus A, B:1, C, E, and F serotypes. Application of the PCR-RE digestion system to clinical samples allowed typing of 34 of 40 clinical samples positive for Ad. The genome type determined by this method was identical to that obtained by traditional RE typing of full-length Ad DNA. The remaining six samples were positive only after a nested PCR. Therefore, to reduce the risk of false-negative results, samples scored negative by the PCR-RE digestion system should be evaluated by the described nested PCR. Used in combination, the PCR-RE digestion method and the nested PCR provide a reliable and sensitive system that can easily be applied to all kinds of clinical samples when rapid identification of adenoviruses is needed.

  • 18.
    Allard, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Enteric adenovirus type 41: genome organization and specific detection procedures1992Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Enteric adenoviruses (EAd) types 40 and 41 (Ad40 and Ad41) representing subgenus F, are primary pathogens of children being second only to rotaviruses as the most important cause of infantile diarrhea.

    The EAds differ from all other adenoviruses in their inability to grow in most conventional established cell lines and have been suggested to be deficient in some early gene functions since they could be complemented by Ad 5 early regions EIA and E1B. In order to search for differences that could explain its characteristic growth restriction, the early regions EIA and E1B of Ad41 (strain D389) were sequenced, analysed and compared with the corresponding regions of Adl2, Ad7, Ad2, and Ad4. As revealed by the analysis of Ad2, three major mRNAs of 9S, 12S and 13S are generated from region EIA. The EIA region of Ad41 encodes two mRNAs corresponding to the 12S and 13S mRNAs. Only the 13S mRNA is transcribed at detectable levels. This mRNA can be translated into a 251 aa putative protein that contains the three highly conserved domains found in all other human adenoviruses and shown to be responsible for many important regulatory functions during infection.

    The E1B region of Ad41 encodes three transcripts that correspond to 22S, 14S and 9S mRNA of Ad2. No equivalent to the 13S mRNA of Ad2 E1B is found. In addition the Ad41 14S mRNA exhibits an additional exon of 23 bp created by a donor and an acceptor splice sites not desribed for other adenovirus E1B sequences.

    Due to their growth restriction in conventional cultures, rapid diagnostic procedures developed for the enteric adenovirus infections have mainly been aimed at the detection of viral antigens or nucleic acids. This thesis also describes several procedures developed for the general detection of adenoviruses and specific detection of the enteric types in stools specimens. General and specific hybridization assays were developed by use of two BamHI clones obtained from the EIA region of Ad41. One- and two-step PCR procedures were also developed for the general detection of adenoviruses using primers corresponding to highly conserved sequences within the hexon gene. Subgenus F specific one- and two-step PCRs were developed by using primers located in the Ad41 E1B region.

    The one-step PCR systems were tested and validated against isolation in tissue culture, DNA restriction enzyme analysis and a commercial latex agglutination test in the study of 60 specimens obtained from children with rotavirus negative diarrhea. The asymptomatic fecal excretion of adenoviruses was evaluated by two-step PCR amplifications on samples from 50 healthy children, 50 healthy adults, and 50 adults suffering from diarrhea.

    Finally, a simplified procedure for detection, discrimination and typing of EAd was also designed by combining the one-step PCR amplification of the hexon region with the restriction of the 300 bp product.

  • 19.
    Andersson, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Human adenoviruses: new bioassays for antiviral screening and CD46 interaction2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Adenoviruses are common pathogens all over the world. The majority of the population has at some point been infected with an adenovirus. Although severe disease can occur in otherwise healthy individuals an adenovirus infection is most commonly self limited in these cases. For immunocompromised individuals however, adenoviruses can be life-threatening pathogens capable of causing disseminated disease and multiple organ failure. Still there is no approved drug specific for treatment of adenovirus infections. We have addressed this using a unique whole cell viral replication reporter gene assay to screen small organic molecules for anti-adenoviral effect. This RCAd11pGFP-vector based assay allowed screening without any preconceived idea of the mechanism for adenovirus inhibition. As a result of the screening campaign 2-[[2-(benzoylamino)benzoyl]amino]-benzoic acid turned out to be a potent inhibitor of adenoviral replication. To establish a structure-activity relationship a number of analogs were synthesized and evaluated for their anti-adenoviral effect. The carboxylic acid moiety of the molecule was important for efficient inhibition of adenovirus replication.

    There are 54 adenovirus types characterized today and these are divided into seven species, A-G. The receptors used by species B and other adenoviruses are not fully characterized. CD46 is a complement regulatory molecule suggested to be used by all species B types and some species D types but this is not established. We have designed a new bioassay for assessment of the interaction between adenoviruses and CD46 and investigated the CD46-binding capacity of adenovirus types indicated to interact with CD46. We concluded that Ad11p, Ad34, Ad35, and Ad50 clearly bind CD46 specifically, whereas Ad3p, Ad7p, Ad14, and Ad37 do not.

    CD46 is expressed on all human nucleated cells and serves as a receptor for a number of different bacteria and viruses. Downregulation of CD46 on the cell surface occurs upon binding by some of these pathogens. We show that early in infection Ad11p virions downregulate CD46 upon binding to a much higher extent than the complement regulatory molecules CD55 and CD59.

    These findings may lead to a better understanding of the pathogenesis of adenoviruses in general and species B adenoviruses in particular and hopefully we have discovered a molecule that can be the basis for development of new anti-adenoviral drugs.

  • 20.
    Andersson, Emma K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Mei, Ya-Fang
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Adenovirus interactions with CD46 on transgenic mouse erythrocytes2010Inngår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 402, nr 1, 20-25 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hemagglutination is an established method but has not been used previously to determine the efficacy of virus binding to a specific cellular receptor. Here we have utilized CD46-expressing erythrocytes from a transgenic mouse to establish whether and to what extent the species B adenoviruses (Ads) as well as Ad37 and Ad49 of species D can interact with CD46. A number of different agglutination patterns, and hence CD46 interactions, could be observed for the different adenovirus types. In this system Ad7p, Ad11a, and Ad14 did not agglutinate mouse erythrocytes at all. Hemagglutination of CD46 expressing erythrocytes with high efficiency was observed for the previously established CD46 users Ad11p and Ad35 as well as for the less investigated Ad34. Ad50 agglutinated with moderate efficiency. Ad16, Ad21 and Ad49 gave incomplete agglutination. Ad16 was the only adenovirus that could be eluted. No specific CD46 interaction could be observed for Ad3p or for Ad37.

  • 21.
    Andersson, Emma K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Strand, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Edlund, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lindman, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Enquist, Per-Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Spjut, Sara
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Allard, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Elofsson, Mikael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Mei, Ya-Fang
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Small molecule screening using a whole cell viral replication reporter gene assay identifies 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid as a novel anti-adenoviral compound2010Inngår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 54, nr 9, 3871-3877 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their anti-adenoviral effect give inconsistent results. We have developed a whole cell-based assay for high-throughput screening of potential anti-adenoviral compounds. The assay is unique in that it is based on a replication competent adenovirus type 11p GFP-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expression in vitro by >/= 80% but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-[[2-(benzoylamino)benzoyl]amino]-benzoic acid, turned out to be a potent inhibitor of adenovirus replication.

  • 22. Andersson, Ida
    et al.
    Simon, Melinda
    Lundkvist, Ake
    Nilsson, Mikael
    Holmström, Anna
    Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Mirazimi, Ali
    Role of actin filaments in targeting of Crimean Congo hemorrhagic fever virus nucleocapsid protein to perinuclear regions of mammalian cells.2004Inngår i: J Med Virol, ISSN 0146-6615, Vol. 72, nr 1, 83-93 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 23.
    Andersson, Simon
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Binding of Norovirus-like particles to integrin expressing CHO cells2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 24. Aoki, Koki
    et al.
    Benkö, Mária
    Davison, Andrew J
    De Jong, Jan C
    Echavarria, Marcela
    Erdman, Dean D
    Harrach, Balázs
    Kajon, Adriana E
    Schnurr, David
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Towards an integrated human adenovirus designation system that utilizes molecular and serological data and serves both clinical and fundamental virology2011Inngår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 85, nr 11, 5703-5704 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 25. Aplander, Karolina
    et al.
    Marttila, Marko
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Manner, Sophie
    Arnberg, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Sterner, Olov
    Ellervik, Ulf
    Molecular wipes: application to epidemic keratoconjuctivitis2011Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 54, nr 19, 6670-6675 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epidemic keratoconjunctivitis (EKC) is a severe disease of the eye, caused by members of the Adenoviridae (Ad) family, with symptoms such as keratitis, conjunctivitis, pain, edema, and reduced vision that may last for months or years. There are no vaccines or antiviral drugs available to prevent or treat EKC. It was found previously that EKC-causing Ads use sialic acid as a cellular receptor and demonstrated that soluble, sialic acid-containing molecules can prevent infection. In this study, multivalent sialic acid constructs based on 10,12-pentacosadiynoic acid (PDA) have been synthesized, and these constructs are shown to be efficient inhibitors of Ad binding (IC(50) = 0.9 mu M) and Ad infectivity (IC(50) = 0.7 mu M). The mechanism of action is to aggregate virus particles and thereby prevent them from binding to ocular cells. Such formulations may be used for topical treatment of adenovirus-caused EKC.

  • 26.
    Arnberg, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Adenovirus E3 protein modulates leukocyte functions2013Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, nr 50, 19976-19977 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 27.
    Arnberg, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Adenovirus receptors: implications for targeting of viral vectors2012Inngår i: TIPS - Trends in Pharmacological Sciences, ISSN 0165-6147, E-ISSN 1873-3735, Vol. 33, nr 8, 442-448 s.Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Cancer, cardiovascular disease, and infectious diseases are all global health threats. To combat these diseases with gene therapies, adenovirus-based vectors have been developed. Although certain clinical trials appear successful, there is an obvious need to improve the efficacy of most adenovirus-based vectors. For the most commonly used vector (based on type 5; Ad5), a main problem is its accumulation in the liver, which can be attributed to interactions with specific host factors. The diverse tropism for types other than Ad5 implies that vectors based on alternative types could have advantages. The numerous interactions of different adenoviruses with host molecules - such as the recently identified desmoglein-2 receptor - may cause novel and unexpected obstacles, but also may provide possibilities for vectors based on alternative types. This review provides an update of new and previously known molecules that mediate cellular attachment of human adenoviruses and discusses how these may influence the targeting of adenovirus-based vectors.

  • 28.
    Arnberg, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Adenovirus receptors: implications for tropism, treatment and targeting2009Inngår i: Reviews in Medical Virology, ISSN 1052-9276, E-ISSN 1099-1654, Vol. 19, nr 3, 165-178 s.Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Adenoviruses (Ads) are the most frequently used viral vectors in gene therapy and cancer therapy. Obstacles to successful clinical application include accumulation of vector and transduction in liver cells, coupled with poor transduction of target cells and tissues such as tumours. Many host molecules, including coagulation factor X, have been identified and suggested to serve as mediators of Ad liver tropism. This review summarises current knowledge concerning these molecules and the mechanisms used by Ads to bind to target cells, and considers the prospects of designing vectors that have been detargeted from the liver and retargeted to cells and tissues of interest in the context of gene therapy and cancer therapy.

  • 29.
    Arnberg, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Edlund, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Kidd, Alistair H
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Adenovirus type 37 uses sialic acid as a cellular receptor2000Inngår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 74, nr 1, 42-48 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two cellular receptors for adenovirus, coxsackievirus-adenovirus receptor (CAR) and major histocompatibility complex class I (MHC-I) alpha2, have recently been identified. In the absence of CAR, MHC-I alpha2 has been suggested to serve as a cellular attachment protein for subgenus C adenoviruses, while members from all subgenera except subgenus B have been shown to interact with CAR. We have found that adenovirus type 37 (Ad37) attachment to CAR-expressing CHO cells was no better than that to CHO cells lacking CAR expression, suggesting that CAR is not used by Ad37 during attachment. Instead, we have identified sialic acid as a third adenovirus receptor moiety. First, Ad37 attachment to both CAR-expressing CHO cells and MHC-I alpha2-expressing Daudi cells was sensitive to neuraminidase treatment, which eliminates sialic acid on the cell surface. Second, Ad37 attachment to sialic acid-expressing Pro-5 cells was more than 10-fold stronger than that to the Pro-5 subline Lec2, which is deficient in sialic acid expression. Third, neuraminidase treatment of A549 cells caused a 60% decrease in Ad37 replication in a fluorescent-focus assay. Moreover, the receptor sialoconjugate is most probably a glycoprotein rather than a ganglioside, since Ad37 attachment to sialic acid-expressing Pro-5 cells was sensitive to protease treatment. Ad37 attachment to Pro-5 cells occurs via alpha(2-->3)-linked sialic acid saccharides rather than alpha(2-->6)-linked ones, since (i) alpha(2-->3)-specific but not alpha(2-->6)-specific lectins blocked Ad37 attachment to Pro-5 cells and (ii) pretreatment of Pro-5 cells with alpha(2-->3)-specific neuraminidase resulted in decreased Ad37 binding. Taken together, these results suggest that, unlike Ad5, Ad37 makes use of alpha(2-->3)-linked sialic acid saccharides on glycoproteins for entry instead of using CAR or MHC-I alpha2.

  • 30.
    Arnberg, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Kidd, Alistair H
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Edlund, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Nilsson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Pring-Åkerblom, Patricia
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Adenovirus type 37 binds to cell surface sialic acid through a charge-dependent interaction2002Inngår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 302, nr 1, 33-43 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Most adenoviruses use the coxsackie-adenovirus receptor (CAR) as a major cellular receptor. We have shown recently that adenovirus types 8, 19a, and 37, which are the major causes of epidemic keratoconjunctivitis, use sialic acid rather than CAR as a major cellular receptor. The predicted isoelectric point of the receptor-interacting knob domain in the adenovirus fiber protein is unusually high (9.0-9.1) in type 8, 19a, and 37. The pKa of sialic acid is low, 2.6, implying a possible involvement of charge in fiber knob-sialic acid interactions. Here we show that (i) positively charged adenovirus knobs require sialic acid for efficient cell membrane interactions; (ii) viral and knob interactions with immobilized sialic acid or cell-surface sialic acid are sensitive to increased ionic strength; (iii) negatively charged molecules such as sulfated glycosaminoglycans inhibit the binding of virions to target cells in a nonspecific, charge-dependent manner; and that (iv) the ability of adenovirus knobs to interact with sialic acid correlates with the overall charge on the top surface of the respective knobs as predicted by homology modeling. Taken together, the results presented provide strong evidence for a charge mechanism during the interaction between the Ad37 fiber knob and sialic acid.

  • 31.
    Arnberg, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Kidd, Alistair H
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Edlund, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Olfat, Farzad
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Initial interactions of subgenus D adenoviruses with A549 cellular receptors: sialic acid versus alpha(v) integrins2000Inngår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 74, nr 16, 7691-3 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Selected members of the adenovirus family have been shown to interact with the coxsackie adenovirus receptor, alpha(v) integrins, and sialic acid on target cells. Initial interactions of subgenus D adenoviruses with target cells have until now been poorly characterized. Here, we demonstrate that adenovirus type 8 (Ad8), Ad19a, and Ad37 use sialic acid as a functional cellular receptor, whereas the Ad9 and Ad19 prototypes do not.

  • 32.
    Arnberg, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Mei, Ya Fang
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Fiber genes of adenoviruses with tropism for the eye and the genital tract1997Inngår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 227, nr 1, 239-244 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have characterized the fibergenes of adenovirus type 19p (Ad19p), Ad19a, and Ad37 by sequencing. The fiber genes of Ad19a and Ad37 are identical and only five amino acids differ comparing Ad19a/Ad37 with Ad19p. Based on the translated sequences we calculated the isoelectrical points (Ips) and found that the fiber knobs of Ad19p, Ad19a, and Ad37 together with Ad8 display the highest Ips of all so far characterized. Two regions within the fiber knob with unusually basic characteristics have been identified. Sequence alignments revealed that the corresponding regions in other fiber knobs are highly antigenic in pepscan analysis and of importance for hemagglutination. Only two positions differ in the knobs comparing Ad19a/Ad37 with Ad19p. Hence, either of these or both amino acid residues should be expected to be responsible for the observed differences in hemagglutination between Ad19p and Ad19a/Ad37. Moreover, we have found two amino acids (Ala227 and Lys252) that are unique in their respective position in Ad19p, Ad19a, Ad37, and Ad8. Three amino acids (Lys236, Lys240, and Asn251) are unique in their respective position in Ad19a and Ad37, that manifest a tropism for the genital tract. All five amino acids colocalize within one of the two basic regions.

  • 33.
    Arnberg, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Pring-Akerblom, Patricia
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Adenovirus type 37 uses sialic acid as a cellular receptor on Chang C cells2002Inngår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 76, nr 17, 8834-8841 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epidemic keratoconjunctivitis (EKC) is a severe eye infection caused mainly by adenovirus type 8 (Ad8), Ad19, and Ad37. We have shown that the EKC-causing adenoviruses use sialic acid as a cellular receptor on A549 cells instead of the coxsackie-adenovirus receptor, which is used by most adenoviruses. Recently, Wu et al. (Virology 279:78-89, 2001) proposed that Ad37 uses a 50-kDa protein as a receptor on Chang C conjunctival cells and that this interaction is independent of sialic acid. According to the American Type Culture Collection, this cell line carries HeLa cell markers and should be considered to be a genital cell line. This prompted us to investigate the function of sialic acid as a cellular receptor for Ad37 in Chang C cells. In this study, we demonstrate that enzymatic removal or lectin-mediated blocking of cell surface sialic acid inhibits the binding of Ad37 virions to Chang C cells, as does soluble, virion-interacting sialic acid-containing substances. The binding was Ca2+ or Mg2+ ion independent and mediated by the knob domain of the trimeric viral fiber polypeptide. Moreover, Ad37 virions infected Chang C cells and two other genital cell lines (HeLa and SiHa) as well as a corneal cell line in a strictly sialic acid-dependent manner. From these results, we conclude that Ad37 uses sialic acid as a major receptor in cell lines derived from both genital and corneal tissues.

  • 34. Asghar, Naveed
    et al.
    Lee, Yi-Ping
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Nilsson, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Lindqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Melik, Wessam
    Kröger, Andrea
    Överby, Anna K.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Johansson, Magnus
    The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 39265Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The tick-borne encephalitis virus (TBEV) is a flavivirus transmitted to humans, usually via tick bites. The virus causes tick-borne encephalitis (TBE) in humans, and symptoms range from mild flu-like symptoms to severe and long-lasting sequelae, including permanent brain damage. It has been suggested that within the population of viruses transmitted to the mammalian host, quasispecies with neurotropic properties might become dominant in the host resulting in neurological symptoms. We previously demonstrated the existence of TBEV variants with variable poly(A) tracts within a single blood-fed tick. To characterize the role of the poly(A) tract in TBEV replication and virulence, we generated infectious clones of Toro-2003 with the wild-type (A)(3)C(A)(6) sequence (Toro-6A) or with a modified (A)(3)C(A)(38) sequence (Toro-38A). Toro-38A replicated poorly compared to Toro-6A in cell culture, but Toro-38A was more virulent than Toro-6A in a mouse model of TBE. Next-generation sequencing of TBEV genomes after passaging in cell culture and/or mouse brain revealed mutations in specific genomic regions and the presence of quasispecies that might contribute to the observed differences in virulence. These data suggest a role for quasispecies development within the poly(A) tract as a virulence determinant for TBEV in mice.

  • 35. Asghar, Naveed
    et al.
    Lindblom, Pontus
    Melik, Wessam
    Lindqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Haglund, Mats
    Forsberg, Pia
    Överby, Anna K.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Andreassen, Åshild
    Lindgren, Per-Eric
    Johansson, Magnus
    Tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance2014Inngår i: PLoS ONE, ISSN 1932-6203, Vol. 9, nr 7, e103264- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A) 3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A) 3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the resequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

  • 36.
    Baudin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Rift Valley fever: consequences of virus-host interactions2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Rift Valley fever virus (RVFV) is a mosquito-borne virus which has the ability to infect a large variety of animals including humans in Africa and Arabian Peninsula. The abortion rate among these animals are close to 100%, and young animals develop severe disease which often are lethal.

    In humans, Rift Valley fever (RVF) presents in most cases as a mild illness with influenza-like symptoms. However, in about 8% of the cases it progresses into a more severe disease with a high case fatality rate. Since there is such a high abortion rate among infected animals, a link between human miscarriage and RVFV has been suggested, but never proven.

    We could in paper I for the first time show an association between acute RVFV infection and miscarriage in humans. We observed an increase in pregnant women arriving at the Port Sudan Hospital with fever of unknown origin, and several of the patients experienced miscarriage. When we analysed their blood samples for several viral diseases we found that many had an acute RVFV infection and of these, 54% experienced a miscarriage. The odds of having a miscarriage was 7 times higher for RVFV patients compared to the RVFV negative women of which only 12% miscarried. These results indicated that RVFV infection could be a contributing factor to miscarriage.

    RVFV is an enveloped virus containing the viral glycoproteins n and c (Gn and Gc respectively), where Gn most likely is responsible for the initial cellular contact. The protein DC-SIGN on dendritic cells and the glycosaminoglycan heparan sulfate has been suggested as cellular receptors for RVFV, however other mechanisms are probably also involved in binding and entry. Charge is a driving force for molecular interaction and has been shown to be important for cellular attachment of several viruses, and in paper II we could show that when the charge around the cells was altered, the infection was affected. We also showed that Gn most likely has a positive charge at a physiological pH.

    When we added negatively charged molecules to the viral particles before infection, we observed a decreased infection efficiency, which we also observed after removal of carbohydrate structures from the cell surface.

    Our results suggested that the cellular interaction partner for initial attachment is a negatively charged carbohydrate. Further investigations into the mechanisms of RVFV cellular interactions has to be undertaken in order to understand, and ultimately prevent, infection and disease.

    There is currently no vaccine approved for human use and no specific treatments for RVF, so there is a great need for developing safe effective drugs targeting this virus. We designed a whole-cell based high-throughput screen (HTS) assay which we used to screen libraries of small molecular compounds for anti-RVFV properties. After dose-response and toxicity analysis of the initial hits, we identified six safe and effective inhibitors of RVFV infection that with further testing could become drug candidates for treatment of RVF. This study demonstrated the application of HTS using a whole-cell virus replication reporter gene assay as an effective method to identify novel compounds with potential antiviral activity against RVFV.

  • 37.
    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) (Annet vitenskapelig)
    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.

  • 38.
    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 study2016Inngår i: The Lancet Global Health, ISSN 2352-3026, E-ISSN 2214-109X, Vol. 4, nr 11, e864-e871 s.Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 39.
    Berg, Hannah
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Mosquito-borne viruses in northern Sweden2016Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 40.
    Bergh Drott, Johanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Alexeyev, Oleg
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Bergström, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Olsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Propionibacterium acnes infection induces upregulation of inflammatory genes and cytokine secretion in prostate epithelial cells2010Inngår i: BMC Microbiology, ISSN 1471-2180, Vol. 10, 126- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The immune stimulating bacterium Propionibacterium acnes is a frequent colonizer of benign and malignant prostate tissue. To understand the pathogenesis of the earliest phase of this infection, we examined the P. acnes triggered immune response in cultivated prostate epithelial cells.

    Results: Prostate epithelial cells are triggered to secrete IL-6, IL-8 and GM-CSF when infected with P. acnes. The secretion of cytokines is accompanied by NFκB related upregulation of the secreted cytokines as well as several components of the TLR2-NFκB signaling pathway.

    Conclusions: P. acnes has potential to trigger a strong immune reaction in the prostate glandular epithelium. Upon infection of prostate via the retrograde urethral route, the induced inflammatory reaction might facilitate bacterial colonization deeper in the prostate tissue where persistent inflammation may impact the development of prostate diseases as hyperplasia and/or malignancy.

  • 41.
    Bergh, Johanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Marklund, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Gustavsson, C
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wiklund, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Grönberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Allard, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Alexeyev, Olog
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    No link between viral findings in the prostate and subsequent cancer development2007Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 96, nr 1, 137-139 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In an investigation of 201 prostate tissue samples from patients with benign prostate hyperplasia that later progressed to prostate cancer and 201 matched controls that did not, there were no differences in the prevalence of adenovirus, herpesvirus, papilloma virus, polyoma virus and Candida albicans DNA.

  • 42.
    Bergh, Johanna
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Marklund, Ingrid
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Virologi.
    Thellenberg-Karlsson, Camilla
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Grönberg, Henrik
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Elgh, Fredrik
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Alexeyev, Oleg A
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Detection of Escherichia coli 16S RNA and Cytotoxic Necrotizing Factor 1 Gene in Benign Prostate Hyperplasia.2007Inngår i: Eur Urol, ISSN 0302-2838, Vol. 51, nr 2, 457-463 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 43.
    Berglin, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Johansson, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sundin, U
    Jidell, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hallmans, Göran
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset.2006Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, nr 4, 453-458 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression. METHODS: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified. RESULTS: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis. CONCLUSIONS: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.

  • 44.
    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 factors2016Inngår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 16, 566Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 45.
    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 Sweden2011Konferansepaper (Annet vitenskapelig)
  • 46.
    Björkman, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Finns det ett samband mellan självkänsla och sexuell risk hos svenska universitetsstudenter?: Självkänsla och stress inverkan på benägenheten att ha oskyddat sex - en populationsstudie i enkätform2016Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 47. 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 hantavirus2011Inngår i: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 208, nr 1, 13-21 s.Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 48.
    Björkstén, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    The nitroblue tetrazolium (NBT) test: a methodological and clinical study1974Doktoravhandling, med artikler (Annet vitenskapelig)
  • 49. Björndal, Asa Szekely
    et al.
    Szekely, Laszlo
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Ebola virus infection inversely correlates with the overall expression levels of promyelocytic leukaemia (PML) protein in cultured cells2003Inngår i: BMC Microbiology, ISSN 1471-2180, Vol. 3, 6- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have established a simple fixation and immunofluorescence staining procedure that allows specific co-detection and precise sub-cellular localization of the PML nuclear bodies and the Ebola virus encoded proteins NP, VP35 and VP40 in formaldehyde treated cells. Interferon-alpha treatment delays virus production in vitro. Intact PML bodies may play an anti-viral role in Ebola infected cells.

  • 50. Blusch, Jürgen H
    et al.
    Deryckere, François
    Windheim, Mark
    Ruzsics, Zsolt
    Arnberg, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Adrian, Thomas
    Burgert, Hans-Gerhard
    The novel early region 3 protein E3/49K is specifically expressed by adenoviruses of subgenus D: implications for epidemic keratoconjunctivitis and adenovirus evolution2002Inngår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 296, nr 1, 94-106 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The early transcription unit 3 (E3) of adenoviruses (Ads) encodes immunomodulatory functions. We previously described a novel gene of 49K within the E3 region of Ad19a, an Ad of subgenus D that is similar to Ad8 and Ad37 causes epidemic keratoconjunctivitis (EKC). Interestingly, 49K was reported not to be present in Ad9 and Ad17, other subgenus D Ads not causing EKC. Therefore, we investigated whether 49K is selectively expressed in EKC-causing Ads. Using specific DNA probes, we detect 49K-homologous genes in all subgenus D Ads tested. Moreover, 49K-specific antibodies recognize a high molecular weight protein in cells infected with all subgenus D serotypes irrespective of their ability to cause EKC. Sequencing of several 49K genes reveals a high homology without a distinct feature recognizable for those of EKC-associated Ad strains. Thus, E3/49K is a subgenus D specific E3 protein whose expression does not correlate with the EKC-causing phenotype and thus may rather be implicated in illnesses commonly caused by this subgenus. Interestingly, the 49K sequences of Ad19a and Ad37 are identical. To estimate the extent of the sequence identity between these two viruses, we initially sequenced the right ITR and the hexon. This analysis revealed that the right ITR of Ad19a is identical to Ad37, while the hexon sequence is Ad19p-like. This suggested that the region of identity is much larger and that Ad19a arose by recombination of Ad37 with an Ad19p-like Ad. Further sequencing mapped the crossover within the DNA binding protein. Thus, Ad19a contains a large sequence block ( approximately 13 kb), from the 100K gene to the right ITR, identical to Ad37. The implications of these findings in light of the temporal appearance of the EKC-causing Ad strains are discussed.

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