PA-X is a virulence factor in avian H9N2 influenza virus
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...
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| Format: | Article |
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Microbiology Society
2015
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| Online Access: | https://eprints.nottingham.ac.uk/43997/ |
| _version_ | 1848796813548584960 |
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| author | Gao, Huijie Liu, Jinhua Kong, Weili Sun, Honglei Pu, Juan Chang, Kin-Chow Xu, Guanlong Sun, Yipeng Qi, Lu Wang, Jinliang |
| author_facet | Gao, Huijie Liu, Jinhua Kong, Weili Sun, Honglei Pu, Juan Chang, Kin-Chow Xu, Guanlong Sun, Yipeng Qi, Lu Wang, Jinliang |
| author_sort | Gao, Huijie |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:53:57Z |
| format | Article |
| id | nottingham-43997 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:53:57Z |
| publishDate | 2015 |
| publisher | Microbiology Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-439972020-05-04T17:14:03Z https://eprints.nottingham.ac.uk/43997/ 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 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. Microbiology Society 2015-09-01 Article PeerReviewed Gao, Huijie, Liu, Jinhua, Kong, Weili, Sun, Honglei, Pu, Juan, Chang, Kin-Chow, Xu, Guanlong, Sun, Yipeng, 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 http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000232 doi:10.1099/jgv.0.000232 doi:10.1099/jgv.0.000232 |
| spellingShingle | Gao, Huijie Liu, Jinhua Kong, Weili Sun, Honglei Pu, Juan Chang, Kin-Chow Xu, Guanlong Sun, Yipeng Qi, Lu Wang, Jinliang PA-X is a virulence factor in avian H9N2 influenza virus |
| title | PA-X is a virulence factor in avian H9N2 influenza virus |
| title_full | PA-X is a virulence factor in avian H9N2 influenza virus |
| title_fullStr | PA-X is a virulence factor in avian H9N2 influenza virus |
| title_full_unstemmed | PA-X is a virulence factor in avian H9N2 influenza virus |
| title_short | PA-X is a virulence factor in avian H9N2 influenza virus |
| title_sort | pa-x is a virulence factor in avian h9n2 influenza virus |
| url | https://eprints.nottingham.ac.uk/43997/ https://eprints.nottingham.ac.uk/43997/ https://eprints.nottingham.ac.uk/43997/ |