Molecular basis of efficient replication and pathogenicity of H9N2 avian influenza viruses in mice

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dc.contributor.author Li, Xiaokang
dc.contributor.author Qi, Wenbao
dc.contributor.author He, Jun
dc.contributor.author Ning, Zhangyong
dc.contributor.author Hu, Yue
dc.contributor.author Tian, Jin
dc.contributor.author Jiao, Peirong
dc.contributor.author Xu, Chenggang
dc.contributor.author Chen, Jianxin
dc.contributor.author Richt, Juergen A.
dc.contributor.author Ma, Wenjun
dc.contributor.author Liao, Ming
dc.date.accessioned 2012-08-03T19:24:41Z
dc.date.available 2012-08-03T19:24:41Z
dc.date.issued 2012-08-03
dc.identifier.uri http://hdl.handle.net/2097/14125
dc.description.abstract H9N2 subtype avian influenza viruses (AIVs) have shown expanded host range and can infect mammals, such as humans and swine. To date the mechanisms of mammalian adaptation and interspecies transmission of H9N2 AIVs remain poorly understood. To explore the molecular basis determining mammalian adaptation of H9N2 AIVs, we compared two avian field H9N2 isolates in a mouse model: one (A/chicken/Guangdong/TS/2004, TS) is nonpathogenic, another one (A/ chicken/Guangdong/V/2008, V) is lethal with efficient replication in mouse brains. In order to determine the basis of the differences in pathogenicity and brain tropism between these two viruses, recombinants with a single gene from the TS (or V) virus in the background of the V (or TS) virus were generated using reverse genetics and evaluated in a mouse model. The results showed that the PB2 gene is the major factor determining the virulence in the mouse model although other genes also have variable impacts on virus replication and pathogenicity. Further studies using PB2 chimeric viruses and mutated viruses with a single amino acid substitution at position 627 [glutamic acid (E) to lysine,(K)] in PB2 revealed that PB2 627K is critical for pathogenicity and viral replication of H9N2 viruses in mouse brains. All together, these results indicate that the PB2 gene and especially position 627 determine virus replication and pathogenicity in mice. This study provides insights into the molecular basis of mammalian adaptation and interspecies transmission of H9N2 AIVs. en_US
dc.relation.uri http://www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0040118 en_US
dc.subject H9N2 en_US
dc.subject Avian influenza viruses (AIVs) en_US
dc.subject Pathogenicity en_US
dc.subject Mice en_US
dc.subject Replication en_US
dc.title Molecular basis of efficient replication and pathogenicity of H9N2 avian influenza viruses in mice en_US
dc.type Article (publisher version) en_US
dc.date.published 2012 en_US
dc.citation.doi doi:10.1371/journal.pone.0040118 en_US
dc.citation.epage e40118 en_US
dc.citation.issue 6 en_US
dc.citation.jtitle PLoS ONE en_US
dc.citation.spage e40118 en_US
dc.citation.volume 7 en_US
dc.contributor.authoreid jricht en_US
dc.contributor.authoreid wjma en_US

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