title: Pathogenicity and transmissibility of novel reassortant H3N2 influenza viruses with 2009 pandemic H1N1 genes in pigs.
abstract: At least 10 different genotypes of novel reassortant H3N2 influenza viruses with 2009 pandemic H1N1 [A(H1N1)pdm09] gene(s) have been identified in U.S. pigs, including the H3N2 variant with a single A(H1N1)pdm09 M gene, which has infected more than 300 people. To date, only three genotypes of these viruses have been evaluated in animal models, and the pathogenicity and transmissibility of the other seven genotype viruses remain unknown. Here, we show that three H3N2 reassortant viruses that contain 3 (NP, M, and NS) or 5 (PA, PB2, NP, M, and NS) genes from A(H1N1)pdm09 were pathogenic in pigs, similar to the endemic H3N2 swine virus. However, the reassortant H3N2 virus with 3 A(H1N1)pdm09 genes and a recent human influenza virus N2 gene was transmitted most efficiently among pigs, whereas the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes was transmitted less efficiently than the endemic H3N2 virus. Interestingly, the polymerase complex of reassortant H3N2 virus with 5 A(H1N1)pdm09 genes showed significantly higher polymerase activity than those of endemic and reassortant H3N2 viruses with 3 A(H1N1)pdm09 genes. Further studies showed that an avian-like glycine at position 228 at the hemagglutinin (HA) receptor binding site is responsible for inefficient transmission of the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes. Taken together, our results provide insights into the pathogenicity and transmissibility of novel reassortant H3N2 viruses in pigs and suggest that a mammalian-like serine at position 228 in the HA is critical for the transmissibility of these reassortant H3N2 viruses.
  
  
  OBJECTIVE
  Swine influenza is a highly contagious zoonotic disease that threatens animal and public health. Introduction of 2009 pandemic H1N1 virus [A(H1N1)pdm09] into swine herds has resulted in novel reassortant influenza viruses in swine, including H3N2 and H1N2 variants that have caused human infections in the United States. We showed that reassortant H3N2 influenza viruses with 3 or 5 genes from A(H1N1)pdm09 isolated from diseased pigs are pathogenic and transmissible in pigs, but the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes displayed less efficient transmissibility than the endemic and reassortant H3N2 viruses with 3 A(H1N1)pdm09 genes. Further studies revealed that an avian-like glycine at the HA 228 receptor binding site of the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes is responsible for less efficient transmissibility in pigs. Our results provide insights into viral pathogenesis and the transmission of novel reassortant H3N2 viruses that are circulating in U.S. swine herds and warrant future surveillance.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Jingjiao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Huigang
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Qinfang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Bawa
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Wenbao
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Duff
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Yuekun
authors.initials: Y
authors.lastname: Lang
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Jianfa
authors.initials: J
authors.lastname: Bai
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Tong
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hesse
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Richt
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA wma@vet.k-state.edu.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ma
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000662:veterinary* / Q000821:virology; D016865:Reassortant Viruses / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology*; D013552:Swine; D013553:Swine Diseases / Q000635:transmission* / Q000821:virology*; D014481:United States
chemical_list: C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus