title: Truncation of C-terminal 20 amino acids in PA-X contributes to adaptation of swine influenza virus in pigs.
abstract: The PA-X protein is a fusion protein incorporating the N-terminal 191 amino acids of the PA protein with a short C-terminal sequence encoded by an overlapping ORF (X-ORF) in segment 3 that is accessed by + 1 ribosomal frameshifting, and this X-ORF exists in either full length or a truncated form (either 61-or 41-condons). Genetic evolution analysis indicates that all swine influenza viruses (SIVs) possessed full-length PA-X prior to 1985, but since then SIVs with truncated PA-X have gradually increased and become dominant, implying that truncation of this protein may contribute to the adaptation of influenza virus in pigs. To verify this hypothesis, we constructed PA-X extended viruses in the background of a "triple-reassortment" H1N2 SIV with truncated PA-X, and evaluated their biological characteristics in vitro and in vivo. Compared with full-length PA-X, SIV with truncated PA-X had increased viral replication in porcine cells and swine respiratory tissues, along with enhanced pathogenicity, replication and transmissibility in pigs. Furthermore, we found that truncation of PA-X improved the inhibition of IFN-I mRNA expression. Hereby, our results imply that truncation of PA-X may contribute to the adaptation of SIV in pigs.
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Guanlong
authors.initials: G
authors.lastname: Xu
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Xuxiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Avian Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, Innovation Team for Pathogen Ecology Research on Animal Influenza Virus, Shanghai, 200241, China.
authors.forename: Qinfang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: He
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Pu
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Hanchun
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Liu
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004285:Dogs; D017930:Genes, Reporter; D057221:Influenza A Virus, H1N2 Subtype / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D007370:Interferon Type I / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D008856:Microscopy, Fluorescence; D009296:Nasal Cavity / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D013553:Swine Diseases / Q000473:pathology* / Q000821:virology; D014132:Trachea / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D007370:Interferon Type I; C573926:PA-X protein, influenza A virus; D011994:Recombinant Proteins; D012097:Repressor Proteins; D017361:Viral Nonstructural Proteins