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

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

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

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

  • 3.
    Johansson, Susanne M C
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Nilsson, Emma C
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Elofsson, Mikael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Ahlskog, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Kihlberg, Jan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Arnberg, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Multivalent sialic acid conjugates inhibit adenovirus type 37 from binding to and infecting human corneal epithelial cells2007Ingår i: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 73, nr 2, s. 92-100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Adenovirus type 37 is one of the main causative agents of epidemic keratoconjunctivitis. In a series of publications, we have reported that this virus uses sialic acid as a cellular receptor. Here we demonstrate in vitro that on a molar basis, multivalent sialic acid conjugated to human serum albumin prevents adenovirus type 37 from binding to and infecting human corneal epithelial cells 1000-fold more efficiently than monosaccharidic sialic acid. We also demonstrate that the extraordinary inhibitory effect of multivalent sialic acid is due to the ability of this compound to aggregate virions. We conclude that multivalent sialic acid may be a potential new antiviral drug, for use in the treatment of epidemic keratoconjunctivitis caused by the adenoviruses that use sialic acid as cellular receptor.

  • 4.
    Mistry, Nitesh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Drobni, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Näslund, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Sunkari, Vivekananda Gupta
    Jenssen, Håvard
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    The anti-papillomavirus activity of human and bovine lactoferricin.2007Ingår i: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 75, nr 3, s. 258-265Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and is necessary for the development of cervical cancer. We have previously found that lactoferrin has antiviral activity against HPV-16 and others have demonstrated that lactoferricin, an N-terminal fragment of lactoferrin, has inhibitory activities against several viruses. Two cell lines and two virus types, HPV-5 and HPV-16, were used to study if lactoferrin and lactoferricin could inhibit HPV pseudovirus (PsV) infection. We demonstrated that bovine lactoferrin (bLf) and human lactoferrin (hLf) were both potent inhibitors of HPV-5 and -16 PsV infections. Among the four lactoferricin derivatives we analyzed, a 15 amino acid peptide from bovine lactoferricin (bLfcin) 17-31 was the most potent inhibitor of both HPV-5 and HPV-16 PsV infection. Among the other derivatives, the human lactoferricin (hLfcin) 1-49 showed some antiviral activity against HPV PsV infection while bLfcin 17-42 inhibited only HPV-5 PsV infection in one of the cell lines. When we studied initial attachment of HPV-16, only bLfcin 17-42 and hLfcin 1-49 had an antiviral effect. This is the first time that lactoferricin was demonstrated to have an inhibitory effect on HPV infection and the antiviral activity differed depending on size, charge and structures of the lactoferricin.

  • 5. Ruzek, Daniel
    et al.
    Zupanc, Tatjana Avsic
    Borde, Johannes
    Chrdle, Ales
    Eyer, Ludek
    Karganova, Galina
    Kholodilov, Ivan
    Knap, Natasa
    Kozlovskaya, Liubov
    Matveev, Andrey
    Miller, Andrew D.
    Osolodkin, Dmitry I.
    Överby, Anna K.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Tikunova, Nina
    Tkachev, Sergey
    Zajkowska, Joanna
    Tick-borne encephalitis in Europe and Russia: review of pathogenesis, clinical features, therapy, and vaccines2019Ingår i: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 164, s. 23-51Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Tick-borne encephalitis (TBE) is an illness caused by tick-borne encephalitis virus (TBEV) infection which is often limited to a febrile illness, but may lead to very aggressive downstream neurological manifestations. The disease is prevalent in forested areas of Europe and northeastern Asia, and is typically caused by infection involving one of three TBEV subtypes, namely the European (TBEV-Eu), the Siberian (TBEV-Sib), or the Far Eastern (TBEV-FE) subtypes. In addition to the three main TBEV subtypes, two other subtypes; i.e., the Baikalian (TBEV-Bkl) and the Himalayan subtype (TBEV-Him), have been described recently. In Europe, TBEV-Eu infection usually results in only mild TBE associated with a mortality rate of < 2%. TBEV-Sib infection also results in a generally mild TBE associated with a non-paralytic febrile form of encephalitis, although there is a tendency towards persistent TBE caused by chronic viral infection. TBE-FE infection is considered to induce the most severe forms of TBE. Importantly though, viral subtype is not the sole determinant of TBE severity; both mild and severe cases of TBE are in fact associated with infection by any of the subtypes. In keeping with this observation, the overall TBE mortality rate in Russia is similar to 2%, in spite of the fact that TBEV-Sib and TBEV-FE subtypes appear to be inducers of more severe TBE than TBEV-Eu. On the other hand, TBEV-Sib and TBEV-FE subtype infections in Russia are associated with essentially unique forms of TBE rarely seen elsewhere if at all, such as the hemorrhagic and chronic (progressive) forms of the disease. For post-exposure prophylaxis and TBE treatment in Russia and Kazakhstan, a specific anti-TBEV immunoglobulin is currently used with well-documented efficacy, but the use of specific TBEV immunoglobulins has been discontinued in Europe due to concerns regarding antibody-enhanced disease in naive individuals. Therefore, new treatments are essential. This review summarizes available data on the pathogenesis and clinical features of TBE, plus different vaccine preparations available in Europe and Russia. In addition, new treatment possibilities, including small molecule drugs and experimental immunotherapies are reviewed. The authors caution that their descriptions of approved or experimental therapies should not be considered to be recommendations for patient care.

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