title: Reassortment between Swine H3N2 and 2009 Pandemic H1N1 in the United States Resulted in Influenza A Viruses with Diverse Genetic Constellations with Variable Virulence in Pigs.
abstract: Repeated spillovers of the H1N1 pandemic virus (H1N1pdm09) from humans to pigs resulted in substantial evolution of influenza A viruses infecting swine, contributing to the genetic and antigenic diversity of influenza A viruses (IAV) currently circulating in swine. The reassortment with endemic swine viruses and maintenance of some of the H1N1pdm09 internal genes resulted in the circulation of different genomic constellations in pigs. Here, we performed a whole-genome phylogenetic analysis of 368 IAV circulating in swine from 2009 to 2016 in the United States. We identified 44 different genotypes, with the most common genotype (32.33%) containing a clade IV-A HA gene, a 2002-lineage NA gene, an M-pdm09 gene, and remaining gene segments of triple reassortant internal gene (TRIG) origin. To understand how different genetic constellations may relate to viral fitness, we compared the pathogenesis and transmission in pigs of six representative genotypes. Although all six genotypes efficiently infected pigs, they resulted in different degrees of pathology and viral shedding. These results highlight the vast H3N2 genetic diversity circulating in U.S. swine after 2009. This diversity has important implications in the control of this disease by the swine industry, as well as a potential risk for public health if swine-adapted viruses with H1N1pdm09 genes have an increased risk to humans, as occurred in the 2011-2012 and 2016 human variant H3N2v cases associated with exhibition swine.
  
  
  
  People continue to spread the 2009 H1N1 pandemic (H1N1pdm09) IAV to pigs, allowing H1N1pdm09 to reassort with endemic swine IAV. In this study, we determined the 8 gene combinations of swine H3N2 IAV detected from 2009 to 2016. We identified 44 different genotypes of H3N2, the majority of which contained at least one H1N1pdm09 gene segment. We compared six representative genotypes of H3N2 in pigs. All six genotypes efficiently infected pigs, but they resulted in different degrees of lung damage and viral shedding. These results highlight the vast genetic diversity of H3N2 circulating in U.S. swine after 2009, with important implications for the control of IAV for the swine industry. Because H1N1pdm09 is also highly adapted to humans, these swine viruses pose a potential risk to public health if swine-adapted viruses with H1N1pdm09 genes also have an increased risk for human infection.
authors.affiliation: Virus and Prion Diseases Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, USA.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Rajão
authors.affiliation: Virus and Prion Diseases Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, USA.
authors.forename: Rasna R
authors.initials: RR
authors.lastname: Walia
authors.affiliation: Virus and Prion Diseases Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Campbell
authors.affiliation: Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Gauger
authors.affiliation: Diagnostic Virology Laboratory, National Veterinary Services Laboratories, Science, Technology and Analysis Services, Veterinary Services, Animal and Plant Health Inspection Service, United States Department of Agriculture, Ames, Iowa, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Janas-Martindale
authors.affiliation: Diagnostic Virology Laboratory, National Veterinary Services Laboratories, Science, Technology and Analysis Services, Veterinary Services, Animal and Plant Health Inspection Service, United States Department of Agriculture, Ames, Iowa, USA.
authors.forename: Mary Lea
authors.initials: ML
authors.lastname: Killian
authors.affiliation: Virus and Prion Diseases Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, USA amy.vincent@ars.usda.gov.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Vincent
mesh_terms: D000818:Animals; D003429:Cross Reactions / Q000276:immunology; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D006385:Hemagglutination Inhibition Tests; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000235:genetics*; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D010802:Phylogeny; D012367:RNA, Viral; D016865:Reassortant Viruses; D013552:Swine; D013553:Swine Diseases / Q000453:epidemiology / Q000821:virology*; D014481:United States / Q000453:epidemiology; D017201:Virus Shedding
chemical_list: D012367:RNA, Viral
keywords: H3N2; genotypes; influenza; pandemic; swine