title: Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity.
abstract: 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.
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, PR 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, PR China.
authors: Honglei
authors: H
authors: Sun
authors: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, PR 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, PR 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, PR 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, PR 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, PR 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, PR 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, PR 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, PR China.
authors: Weili
authors: W
authors: Kong
authors: School of Veterinary Medicine and Science, University of Nottingham - Sutton Bonington Campus, Sutton Bonington, UK.
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, PR China.
authors: Juan
authors: J
authors: Pu
authors: School of Veterinary Medicine and Science, University of Nottingham - Sutton Bonington Campus, Sutton Bonington, UK.
authors: Kin-Chow
authors: KC
authors: Chang
authors: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, PR 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, PR China.
authors: Jinhua
authors: J
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, PR China.
authors: Yipeng
authors: Y
authors: Sun
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D053127:Influenza A Virus, H9N2 Subtype / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D007251:Influenza, Human / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication
chemical_list: C573926:PA-X protein, influenza A virus; D012097:Repressor Proteins; D017361:Viral Nonstructural Proteins