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Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus.


ABSTRACT: The 2009/2010 pandemic influenza virus (H1N1pdm) contains an avian-lineage PB2 gene that lacks E627K and D701N substitutions important in the pathogenesis and transmission of avian-origin viruses in humans or other mammals. Previous studies have shown that PB2-627K is not necessary because of a compensatory Q591R substitution. The role that PB2-701N plays in the H1N1pdm phenotype is not well understood. Therefore, PB2-D701N was introduced into an H1N1pdm virus (A/New York/1682/2009 (NY1682)) and analyzed in vitro and in vivo. Mini-genome replication assay, in vitro replication characteristics in cell lines, and analysis in the mouse and ferret models demonstrated that PB2-D701N increased virus replication rates and resulted in more severe pathogenicity in mice and more efficient transmission in ferrets. In addition, compared to the NY1682-WT virus, the NY1682-D701N mutant virus induced less IFN-? and replicated to a higher titer in primary human alveolar epithelial cells. These findings suggest that the acquisition of the PB2-701N substitution by H1N1pdm viruses may result in more severe disease or increase transmission in humans.

SUBMITTER: Zhou B 

PROVIDER: S-EPMC3683066 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus.

Zhou Bin B   Pearce Melissa B MB   Li Yan Y   Wang Jieru J   Mason Robert J RJ   Tumpey Terrence M TM   Wentworth David E DE  

PloS one 20130614 6


The 2009/2010 pandemic influenza virus (H1N1pdm) contains an avian-lineage PB2 gene that lacks E627K and D701N substitutions important in the pathogenesis and transmission of avian-origin viruses in humans or other mammals. Previous studies have shown that PB2-627K is not necessary because of a compensatory Q591R substitution. The role that PB2-701N plays in the H1N1pdm phenotype is not well understood. Therefore, PB2-D701N was introduced into an H1N1pdm virus (A/New York/1682/2009 (NY1682)) and  ...[more]

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