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

Abstract

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.

Citation

Gao, H., Sun, Y., Hu, J., Qi, L., Wang, J., Xiong, X., …Liu, J. (in press). The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses. Scientific Reports, 5(1), https://doi.org/10.1038/srep08262

• Journal Article Type: Article
• Acceptance Date: Jan 14, 2015
• Online Publication Date: Feb 5, 2015
• Deposit Date: Jul 5, 2017
• Publicly Available Date: Jul 5, 2017
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 1
• DOI: https://doi.org/10.1038/srep08262
• Public URL: https://nottingham-repository.worktribe.com/output/745425
• Publisher URL: https://www.nature.com/articles/srep08262.pdf