The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses

PA-X is a novel protein encoded by PA mRNA and is found to decrease the pathogenicity of pandemic 1918 H1N1 virus in mice. However, the importance of PA-X proteins in current epidemiologically important influenza A virus strains is not known. In this study, we report on the pathogenicity and patholo...

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Main Authors: Gao, Huijie, Sun, Yipeng, Hu, Jiao, Qi, Lu, Wang, Jinliang, Xiong, Xin, Wang, Yu, He, Qiming, Lin, Yang, Kong, Weili, Seng, Lai-Giea, Sun, Honglei, Pu, Juan, Chang, Kin-Chow, Liu, Xiufan, Liu, Jinhua
Format: Article
Published: Nature Publishing Group 2015
Online Access:https://eprints.nottingham.ac.uk/43991/
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author Gao, Huijie
Sun, Yipeng
Hu, Jiao
Qi, Lu
Wang, Jinliang
Xiong, Xin
Wang, Yu
He, Qiming
Lin, Yang
Kong, Weili
Seng, Lai-Giea
Sun, Honglei
Pu, Juan
Chang, Kin-Chow
Liu, Xiufan
Liu, Jinhua
author_facet Gao, Huijie
Sun, Yipeng
Hu, Jiao
Qi, Lu
Wang, Jinliang
Xiong, Xin
Wang, Yu
He, Qiming
Lin, Yang
Kong, Weili
Seng, Lai-Giea
Sun, Honglei
Pu, Juan
Chang, Kin-Chow
Liu, Xiufan
Liu, Jinhua
author_sort Gao, Huijie
building Nottingham Research Data Repository
collection Online Access
description PA-X is a novel protein encoded by PA mRNA and is found to decrease the pathogenicity of pandemic 1918 H1N1 virus in mice. However, the importance of PA-X proteins in current epidemiologically important influenza A virus strains is not known. In this study, we report on the pathogenicity and pathological effects of PA-X deficient 2009 pandemic H1N1 (pH1N1) and highly pathogenic avian influenza H5N1 viruses. We found that loss of PA-X expression in pH1N1 and H5N1 viruses increased viral replication and apoptosis in A549 cells and increased virulence and host inflammatory response in mice. In addition, PA-X deficient pH1N1 and H5N1 viruses up-regulated PA mRNA and protein synthesis and increased viral polymerase activity. Loss of PA-X was also accompanied by accelerated nuclear accumulation of PA protein and reduced suppression of PA on non-viral protein expression. Our study highlights the effects of PA-X on the moderation of viral pathogenesis and pathogenicity.
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spelling nottingham-439912020-05-04T17:03:03Z https://eprints.nottingham.ac.uk/43991/ The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses Gao, Huijie Sun, Yipeng Hu, Jiao Qi, Lu Wang, Jinliang Xiong, Xin Wang, Yu He, Qiming Lin, Yang Kong, Weili Seng, Lai-Giea Sun, Honglei Pu, Juan Chang, Kin-Chow Liu, Xiufan Liu, Jinhua PA-X is a novel protein encoded by PA mRNA and is found to decrease the pathogenicity of pandemic 1918 H1N1 virus in mice. However, the importance of PA-X proteins in current epidemiologically important influenza A virus strains is not known. In this study, we report on the pathogenicity and pathological effects of PA-X deficient 2009 pandemic H1N1 (pH1N1) and highly pathogenic avian influenza H5N1 viruses. We found that loss of PA-X expression in pH1N1 and H5N1 viruses increased viral replication and apoptosis in A549 cells and increased virulence and host inflammatory response in mice. In addition, PA-X deficient pH1N1 and H5N1 viruses up-regulated PA mRNA and protein synthesis and increased viral polymerase activity. Loss of PA-X was also accompanied by accelerated nuclear accumulation of PA protein and reduced suppression of PA on non-viral protein expression. Our study highlights the effects of PA-X on the moderation of viral pathogenesis and pathogenicity. Nature Publishing Group 2015-02-05 Article PeerReviewed Gao, Huijie, Sun, Yipeng, Hu, Jiao, Qi, Lu, Wang, Jinliang, Xiong, Xin, Wang, Yu, He, Qiming, Lin, Yang, Kong, Weili, Seng, Lai-Giea, Sun, Honglei, Pu, Juan, Chang, Kin-Chow, Liu, Xiufan and Liu, Jinhua (2015) The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses. Scientific Reports, 5 (1). p. 8262. ISSN 2045-2322 https://www.nature.com/articles/srep08262.pdf doi:10.1038/srep08262 doi:10.1038/srep08262
spellingShingle Gao, Huijie
Sun, Yipeng
Hu, Jiao
Qi, Lu
Wang, Jinliang
Xiong, Xin
Wang, Yu
He, Qiming
Lin, Yang
Kong, Weili
Seng, Lai-Giea
Sun, Honglei
Pu, Juan
Chang, Kin-Chow
Liu, Xiufan
Liu, Jinhua
The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses
title The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses
title_full The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses
title_fullStr The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses
title_full_unstemmed The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses
title_short The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses
title_sort contribution of pa-x to the virulence of pandemic 2009 h1n1 and highly pathogenic h5n1 avian influenza viruses
url https://eprints.nottingham.ac.uk/43991/
https://eprints.nottingham.ac.uk/43991/
https://eprints.nottingham.ac.uk/43991/