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

• DOI: 10.1038/srep08262
• Publication Date: 2015-02-05T10:23:59Z
• Authors: Huijie Gao; Yipeng Sun; Jiao Hu; Lu Qi; Jinliang Wang; Xin Xiong; Yu Wang; Qiming He; Yang Lin; Weili Kong; Lai-Giea Seng; Honglei Sun; Juan Pu; Kin-Chow Chang; Xiufan Liu; Jinhua Liu
• Keywords: Gene Expression Regulation, Viral; 0303 health sciences; Influenza A Virus, H5N1 Subtype; Virulence; Active Transport, Cell Nucleus; Apoptosis; Virus Replication; Article; Cell Line; 3. Good health; Disease Models, Animal; Mice; Protein Transport; Viral Proteins; 03 medical and health sciences; Influenza A Virus, H1N1 Subtype; Orthomyxoviridae Infections; Protein Biosynthesis; Animals; Humans; Gene Deletion

AbstractPA-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.