title: The origin of the PB1 segment of swine influenza A virus subtype H1N2 determines viral pathogenicity in mice.
abstract: Swine appear to be a key species in the generation of novel human influenza pandemics. Previous pandemic viruses are postulated to have evolved in swine by reassortment of avian, human, and swine influenza viruses. The human pandemic influenza viruses that emerged in 1957 and 1968 as well as swine viruses circulating since 1998 encode PB1 segments derived from avian influenza viruses. Here we investigate the possible role in viral replication and virulence of the PB1 gene segments present in two swine H1N2 influenza A viruses, A/swine/Sweden/1021/2009(H1N2) (sw 1021) and A/swine/Sweden/9706/2010(H1N2) (sw 9706), where the sw 1021 virus has shown to be more pathogenic in mice. By using reverse genetics, we swapped the PB1 genes of these two viruses. Similar to the sw 9706 virus, chimeric sw 1021 virus carrying the sw 9706 PB1 gene was not virulent in mice. In contrast, replacement of the PB1 gene of the sw 9706 virus by that from sw 1021 virus resulted in increased pathogenicity. Our study demonstrated that differences in virulence of swine influenza virus subtype H1N2 are attributed at least in part to the PB1 segment.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. Electronic address: giorgi.metreveli@mssm.edu.
authors.forename: Giorgi
authors.initials: G
authors.lastname: Metreveli
authors.affiliation: Bovine Biologics Research VMRD Zoetis, 333 Portage Street, KZO-300-206.5B, Kalamazoo, MI 49007, USA.
authors.forename: Qinshan
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mena
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Mirco
authors.initials: M
authors.lastname: Schmolke
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Berg
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D057221:Influenza A Virus, H1N2 Subtype / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology*; D011995:Recombination, Genetic; D059386:Reverse Genetics; D013552:Swine; D013553:Swine Diseases / Q000821:virology; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*; D014774:Virulence
chemical_list: D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1
keywords: H1N2; PB1 segment; Reverse genetics; Swine influenza virus; Virulence
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