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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

Authors

Huijie Gao

Jinhua Liu

Weili Kong

Honglei Sun

Juan Pu

KIN-CHOW CHANG kin-chow.chang@nottingham.ac.uk
Professor of Veterinary Molecular Medicine

Guanlong Xu

Yipeng Sun

Lu Qi

Jinliang Wang



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 http://eprints.nottingham.ac.uk/id/eprint/43997
Publisher URL http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000232
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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J.Gen Virol 96(9) 2015 final.pdf (4.8 Mb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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