PA-X is a virulence factor in avian H9N2 influenza virus

Gao, Huijie; Liu, Jinhua; Kong, Weili; Sun, Honglei; Pu, Juan; Chang, Kin-Chow; Xu, Guanlong; Sun, Yipeng; Qi, Lu; Wang, Jinliang

Abstract

H9N2 influenza viruses have been circulating worldwide in multiple avian species, and regularly infect pigs and humans. Recently, a novel protein, PA-X, produced from the PA gene by ribosomal frameshifting, was demonstrated to be an antivirulence factor in pandemic 2009 H1N1, highly pathogenic avian H5N1 and 1918 H1N1 viruses. However, a similar role of PA-X in the prevalent H9N2 avian influenza viruses has not been established. In this study, we compared the virulence and cytopathogenicity of H9N2 WT virus and H9N2 PA-X-deficient virus. Loss of PA-X in H9N2 virus reduced apoptosis and had a marginal effect on progeny virus output in human pulmonary adenocarcinoma (A549) cells. Without PA-X, PA was less able to suppress co-expressed GFP in human embryonic kidney 293T cells. Furthermore, absence of PA-X in H9N2 virus attenuated viral pathogenicity in mice, which showed no mortality, reduced progeny virus production, mild-to-normal lung histopathology, and dampened proinflammatory cytokine and chemokine response. Therefore, unlike previously reported H1N1 and H5N1 viruses, we show that PA-X protein in H9N2 virus is a pro-virulence factor in facilitating viral pathogenicity and that the pro- or antivirulence role of PA-X in influenza viruses is virus strain-dependent.

Citation

Gao, H., Liu, J., Kong, W., Sun, H., Pu, J., Chang, K., …Wang, J. (2015). PA-X is a virulence factor in avian H9N2 influenza virus. Journal of General Virology, 96(9), https://doi.org/10.1099/jgv.0.000232

• Journal Article Type: Article
• Acceptance Date: Jun 26, 2015
• Publication Date: Sep 1, 2015
• Deposit Date: Jul 5, 2017
• Publicly Available Date: Jul 5, 2017
• Journal: Journal of General Virology
• Print ISSN: 0022-1317
• Electronic ISSN: 0022-1317
• Publisher: Microbiology Society
• Peer Reviewed: Peer Reviewed
• Volume: 96
• Issue: 9
• DOI: https://doi.org/10.1099/jgv.0.000232
• Public URL: https://nottingham-repository.worktribe.com/output/757978
• Publisher URL: http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000232