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 in ovo and led to more rapid viral shedding and widespread organ dissemination in vivo 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.
Biotechnology and Biological Sciences Research Council
(Award BB/R012679/1)
Principle Award Recipient:
IqbalMunir
UKRI
(Award BB/S011269/1)
Principle Award Recipient:
IqbalMunir
Biotechnology and Biological Sciences Research Council
(Award BB/L018853/1; BB/S013792/1)
Principle Award Recipient:
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)
This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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