Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity
The PA-X protein, arising from ribosomal frameshift during PA translation, was recently discovered in influenza A virus (IAV). The C-terminal domain ‘X’ of PA-X proteins in IAVs can be classified as full-length (61 aa) or truncated (41 aa). In the main, avian influenza viruses express full-length PA...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
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Microbiology Society
2015
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| Online Access: | https://eprints.nottingham.ac.uk/43998/ |
| _version_ | 1848796813772980224 |
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| author | Gao, Huijie Sun, Yipeng Liu, Xiufan Sun, Honglei Hu, Jiao Wang, Jinliang Lin, Yang Chang, Kin-Chow Wang, Yu Qi, Lu Pu, Juan Xiong, Xin Liu, Jinhua Seng, Lai-Giea Kong, Weili He, Qiming |
| author_facet | Gao, Huijie Sun, Yipeng Liu, Xiufan Sun, Honglei Hu, Jiao Wang, Jinliang Lin, Yang Chang, Kin-Chow Wang, Yu Qi, Lu Pu, Juan Xiong, Xin Liu, Jinhua Seng, Lai-Giea Kong, Weili He, Qiming |
| author_sort | Gao, Huijie |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The PA-X protein, arising from ribosomal frameshift during PA translation, was recently discovered in influenza A virus (IAV). The C-terminal domain ‘X’ of PA-X proteins in IAVs can be classified as full-length (61 aa) or truncated (41 aa). In the main, avian influenza viruses express full-length PA-X proteins, whilst 2009 pandemic H1N1 (pH1N1) influenza viruses harbour truncated PA proteins. The truncated form lacks aa 232–252 of the full-length PA-X protein. The significance of PA-X length in virus function remains unclear. To address this issue, we constructed a set of contemporary influenza viruses (pH1N1, avian H5N1 and H9N2) with full and truncated PA-X by reverse genetics to compare their replication and host pathogenicity. All full-length PA-X viruses in human A549 cells conferred 10- to 100-fold increase in viral replication and 5–8 % increase in apoptosis relative to corresponding truncated PA-X viruses. Full-length PA-X viruses were more virulent and caused more severe inflammatory responses in mice. Furthermore, aa 233–252 at the C terminus of PA-X strongly suppressed co-transfected gene expression by ∼50 %, suggesting that these terminal 20 aa could play a role in enhancing viral replication and contribute to virulence. |
| first_indexed | 2025-11-14T19:53:57Z |
| format | Article |
| id | nottingham-43998 |
| 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-439982020-05-04T17:11:49Z https://eprints.nottingham.ac.uk/43998/ Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity Gao, Huijie Sun, Yipeng Liu, Xiufan Sun, Honglei Hu, Jiao Wang, Jinliang Lin, Yang Chang, Kin-Chow Wang, Yu Qi, Lu Pu, Juan Xiong, Xin Liu, Jinhua Seng, Lai-Giea Kong, Weili He, Qiming The PA-X protein, arising from ribosomal frameshift during PA translation, was recently discovered in influenza A virus (IAV). The C-terminal domain ‘X’ of PA-X proteins in IAVs can be classified as full-length (61 aa) or truncated (41 aa). In the main, avian influenza viruses express full-length PA-X proteins, whilst 2009 pandemic H1N1 (pH1N1) influenza viruses harbour truncated PA proteins. The truncated form lacks aa 232–252 of the full-length PA-X protein. The significance of PA-X length in virus function remains unclear. To address this issue, we constructed a set of contemporary influenza viruses (pH1N1, avian H5N1 and H9N2) with full and truncated PA-X by reverse genetics to compare their replication and host pathogenicity. All full-length PA-X viruses in human A549 cells conferred 10- to 100-fold increase in viral replication and 5–8 % increase in apoptosis relative to corresponding truncated PA-X viruses. Full-length PA-X viruses were more virulent and caused more severe inflammatory responses in mice. Furthermore, aa 233–252 at the C terminus of PA-X strongly suppressed co-transfected gene expression by ∼50 %, suggesting that these terminal 20 aa could play a role in enhancing viral replication and contribute to virulence. Microbiology Society 2015-08-01 Article PeerReviewed Gao, Huijie, Sun, Yipeng, Liu, Xiufan, Sun, Honglei, Hu, Jiao, Wang, Jinliang, Lin, Yang, Chang, Kin-Chow, Wang, Yu, Qi, Lu, Pu, Juan, Xiong, Xin, Liu, Jinhua, Seng, Lai-Giea, Kong, Weili and He, Qiming (2015) Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity. Journal of General Virology, 96 (8). pp. 2036-2049. ISSN 0022-1317 https://doi.org/10.1099/vir.0.000143 doi:10.1099/vir.0.000143 doi:10.1099/vir.0.000143 |
| spellingShingle | Gao, Huijie Sun, Yipeng Liu, Xiufan Sun, Honglei Hu, Jiao Wang, Jinliang Lin, Yang Chang, Kin-Chow Wang, Yu Qi, Lu Pu, Juan Xiong, Xin Liu, Jinhua Seng, Lai-Giea Kong, Weili He, Qiming Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity |
| title | Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity |
| title_full | Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity |
| title_fullStr | Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity |
| title_full_unstemmed | Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity |
| title_short | Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity |
| title_sort | twenty amino acids at the c-terminus of pa-x are associated with increased influenza a virus replication and pathogenicity |
| url | https://eprints.nottingham.ac.uk/43998/ https://eprints.nottingham.ac.uk/43998/ https://eprints.nottingham.ac.uk/43998/ |