|Event Title||First Global Alliance for Research on Avian Diseases (GARAD) Conference|
|Event Date & Time||On Wed, 01 Jul 2015 at 10:30:00 - 10:55:00|
|Venue||Edmond J. Safra Lecture Theatre|
|Abstract Title||Virulence determinants of influenza A virus|
|Affiliations||The Roslin Institute, University of Edinburgh, EH25 9RG, UK|
Influenza A virus is a widespread pathogen of avian and mammalian hosts, with remarkably variable pathogenicity. In gallinaceous poultry, certain strains approach near 100% lethality, while other infections are inapparent. We recently showed that segment 3 of the virus contains a second gene, termed PA-X, whose product functions to repress cellular gene expression. PA-X also modulates IAV virulence in a mouse infection model, acting to decrease pathogenicity. Although most strains of virus are predicted to encode PA-X, strain-dependent variations in shut off activity have been noted; this leads to the question of why the gene is nevertheless highly conserved. We deleted PA-X from both high (avian) and low (laboratory) activity virus strains, finding that loss of PA-X expression in the avian background resulted in increased pathogenicity in mice, but its removal from a laboratory-adapted virus had a lesser effect. However, in chicken embryos, mutation of PA-X led to decreased embryo mortality and lower overall pathology; effects that were more pronounced in the lab strain than the avian virus background. Thus the effects of PA-X on virus pathogenicity are host dependent. Furthermore, the PR8 PA-X protein may harbour a function unrelated to host cell shut off.