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

Gao, Huijie and Liu, Jinhua and Kong, Weili and Sun, Honglei and Pu, Juan and Chang, Kin-Chow and Xu, Guanlong and Sun, Yipeng and Qi, Lu and Wang, Jinliang (2015) PA-X is a virulence factor in avian H9N2 influenza virus. Journal of General Virology, 96 (9). pp. 2587-2594. ISSN 0022-1317

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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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Identification Number: 10.1099/jgv.0.000232
Depositing User: Eprints, Support
Date Deposited: 05 Jul 2017 12:07
Last Modified: 18 Oct 2017 18:25
URI: http://eprints.nottingham.ac.uk/id/eprint/43997

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