title: The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses.
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.
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Huijie
authors: H
authors: Gao
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Yipeng
authors: Y
authors: Sun
authors: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China.
authors: Jiao
authors: J
authors: Hu
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Lu
authors: L
authors: Qi
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Jinliang
authors: J
authors: Wang
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Xin
authors: X
authors: Xiong
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Yu
authors: Y
authors: Wang
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Qiming
authors: Q
authors: He
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Yang
authors: Y
authors: Lin
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Weili
authors: W
authors: Kong
authors: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, United Kingdom.
authors: Lai-Giea
authors: LG
authors: Seng
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Honglei
authors: H
authors: Sun
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Juan
authors: J
authors: Pu
authors: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, United Kingdom.
authors: Kin-Chow
authors: KC
authors: Chang
authors: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China.
authors: Xiufan
authors: X
authors: Liu
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors: Jinhua
authors: J
authors: Liu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D004195:Disease Models, Animal; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000473:pathology / Q000821:virology; D014176:Protein Biosynthesis; D021381:Protein Transport; D014764:Viral Proteins / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D014764:Viral Proteins
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