%0 Journal Article %A Clements, Anabel L. %A Peacock, Thomas P. %A Sealy, Joshua E. %A Lee, Hui Min %A Hussain, Saira %A Sadeyen, Jean-Remy %A Shelton, Holly %A Digard, Paul %A Iqbal, Munir %T PA-X is an avian virulence factor in H9N2 avian influenza virus %D 2021 %J Journal of General Virology, %V 102 %N 3 %@ 1465-2099 %C 001531 %R https://doi.org/10.1099/jgv.0.001531 %K accessory protein %K PA-X %K poultry %K Influenza %K virulence factor %K avian influenza %I Microbiology Society, %X 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001531