tetano
Editor, Senior Moderator
J Gen Virol. 2012 Feb 29. [Epub ahead of print]
In vivo and in vitro studies on the antiviral activities of viperin against influenza H1N1 virus infection.
Tan KS, Olfat F, Phoon MC, Hsu JP, Howe JL, Seet JE, Chin KC, Chow VT.
Source
National University of Singapore;
Abstract
Influenza A virus has caused significant 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 infection in vitro and in vivo. Wild-type HeLa and viperin-expressing HeLa cells were infected with influenza A/WSN/33/H1N1 virus, and subjected to virologic, light and electron microscopic analyses. Viperin expression reduced viral replication and titers, and restricted viral budding. Young and old viperin-knockout mice and wild-type control animals were challenged with influenza A/WSN/33/H1N1 at lethal doses of 103 and 104 plaque-forming units via the intra-tracheal route. Lungs were subjected to histopathologic, virologic, and molecular studies. Upon lethal influenza virus challenge, both wild-type and viperin-knockout mice revealed similar trends of infection and recovery with similar mortality rates. Viral quantification assay and histopathologic 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 did not enhance the viral load nor pulmonary damage in the lungs of infected mice. This may due to the compensation of IFN-stimulated genes in the lungs and/or the influenza NS1-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.
PMID:
22377585
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22377585
In vivo and in vitro studies on the antiviral activities of viperin against influenza H1N1 virus infection.
Tan KS, Olfat F, Phoon MC, Hsu JP, Howe JL, Seet JE, Chin KC, Chow VT.
Source
National University of Singapore;
Abstract
Influenza A virus has caused significant 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 infection in vitro and in vivo. Wild-type HeLa and viperin-expressing HeLa cells were infected with influenza A/WSN/33/H1N1 virus, and subjected to virologic, light and electron microscopic analyses. Viperin expression reduced viral replication and titers, and restricted viral budding. Young and old viperin-knockout mice and wild-type control animals were challenged with influenza A/WSN/33/H1N1 at lethal doses of 103 and 104 plaque-forming units via the intra-tracheal route. Lungs were subjected to histopathologic, virologic, and molecular studies. Upon lethal influenza virus challenge, both wild-type and viperin-knockout mice revealed similar trends of infection and recovery with similar mortality rates. Viral quantification assay and histopathologic 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 did not enhance the viral load nor pulmonary damage in the lungs of infected mice. This may due to the compensation of IFN-stimulated genes in the lungs and/or the influenza NS1-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.
PMID:
22377585
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22377585