title: In vivo and in vitro studies on the antiviral activities of viperin against influenza H1N1 virus infection.
abstract: Influenza A virus has caused a number of pandemics in past decades, including the recent H1N1-2009 pandemic. Viperin is an interferon (IFN)-inducible protein of innate immunity, and acts as a broad-spectrum antiviral protein. We explored the antiviral activities and mechanisms of viperin during influenza virus (IFV) infection in vitro and in vivo. Wild-type (WT) HeLa and viperin-expressing HeLa cells were infected with influenza A/WSN/33/H1N1 (WSN33) virus, and subjected to virological, light and electron microscopic analyses. Viperin expression reduced virus replication and titres, and restricted viral budding. Young and old viperin-knockout (KO) mice and WT control animals were challenged with influenza WSN33 at lethal doses of 10(3) and 10(4) p.f.u. via the intratracheal route. Lungs were subjected to histopathological, virological and molecular studies. Upon lethal IFV challenge, both WT and KO mice revealed similar trends of infection and recovery with similar mortality rates. Viral quantification assay and histopathological evaluation of lungs from different time points showed no significant difference in viral loads and lung damage scores between the two groups of mice. Although the in vitro studies demonstrated the ability of viperin to restrict influenza H1N1 virus replication, the viperin-deficient mouse model indicated that absence of viperin enhanced neither the viral load nor pulmonary damage in the lungs of infected mice. This may be due to the compensation of IFN-stimulated genes in the lungs and/or the influenza non-structural protein 1-mediated IFN antagonism dampening the IFN response, thereby rendering the loss of viperin insignificant. Nevertheless, further investigations that exploit the antiviral mechanisms of viperin as prophylaxis are still warranted.
authors.affiliation: Infectious Diseases Interdisciplinary Research Group, Singapore-Massachusetts Institute of Technology Alliance in Research and Technology, Singapore 117456.|Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Kent Ridge, Singapore 117597.
authors.forename: Kai Sen
authors.initials: KS
authors.lastname: Tan
authors.affiliation: Infectious Diseases Interdisciplinary Research Group, Singapore-Massachusetts Institute of Technology Alliance in Research and Technology, Singapore 117456.
authors.forename: Farzad
authors.initials: F
authors.lastname: Olfat
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Kent Ridge, Singapore 117597.
authors.forename: Meng Chee
authors.initials: MC
authors.lastname: Phoon
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Kent Ridge, Singapore 117597.
authors.forename: Jung Pu
authors.initials: JP
authors.lastname: Hsu
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Kent Ridge, Singapore 117597.
authors.forename: Josephine L C
authors.initials: JLC
authors.lastname: Howe
authors.affiliation: Department of Pathology, National University Hospital, Singapore 119074.
authors.forename: Ju Ee
authors.initials: JE
authors.lastname: Seet
authors.affiliation: Singapore Immunology Network, Immunos, Biopolis, Singapore 138648.
authors.forename: Keh Chuang
authors.initials: KC
authors.lastname: Chin
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Kent Ridge, Singapore 117597.
authors.forename: Vincent T K
authors.initials: VTK
authors.lastname: Chow
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D008168:Lung / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication; D000090123:Viperin Protein
chemical_list: D000998:Antiviral Agents; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; C417529:Rsad2 protein, mouse; D000090123:Viperin Protein; C444427:RSAD2 protein, human