1887

Abstract

Influenza A viruses encode several accessory proteins that have host- and strain-specific effects on virulence and replication. The accessory protein PA-X is expressed due to a ribosomal frameshift during translation of the PA gene. Depending on the particular combination of virus strain and host species, PA-X has been described as either acting to reduce or increase virulence and/or virus replication. In this study, we set out to investigate the role PA-X plays in H9N2 avian influenza viruses, focusing on the natural avian host, chickens. We found that the G1 lineage A/chicken/Pakistan/UDL-01/2008 (H9N2) PA-X induced robust host shutoff in both mammalian and avian cells and increased virus replication in mammalian, but not avian cells. We further showed that PA-X affected embryonic lethality and led to more rapid viral shedding and widespread organ dissemination in chickens. Overall, we conclude PA-X may act as a virulence factor for H9N2 viruses in chickens, allowing faster replication and wider organ tropism.

Funding
This study was supported by the:
  • DigardPaul , Medical Research Council , (Award MR/M011747/1)
  • IqbalMunir , Biotechnology and Biological Sciences Research Council , (Award BB/R012679/1)
  • IqbalMunir , UKRI , (Award BB/S011269/1)
  • IqbalMunir , Biotechnology and Biological Sciences Research Council , (Award BB/L018853/1; BB/S013792/1)
  • IqbalMunir , Biotechnology and Biological Sciences Research Council , (Award BBS/E/I/00001981; BB/R012679/1; BB/P016472/1; BBS/E/I/00007030; BBS/E/I/00007031; BBS/E/I/00007035; BBS/E/I/00007036; BB/P013740/1)
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/content/journal/jgv/10.1099/jgv.0.001531
2021-02-05
2021-02-26
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