title: Effects of PB1-F2 on the pathogenicity of H1N1 swine influenza virus in mice and pigs.
abstract: Although several studies have exploited the effects of PB1-F2 in swine influenza viruses, its contribution to the pathogenicity of swine influenza viruses remains unclear. Herein, we investigated the effects of PB1-F2 on the pathogenicity of influenza virus using a virulent H1N1 A/swine/Kansas/77778/2007 (KS07) virus, which expresses a full-length PB1-F2, in mice and pigs. Using reverse genetics, we generated the wild-type KS07 (KS07_WT), a PB1-F2 knockout mutant (KS07_K/O) and its N66S variant (KS07_N66S). KS07_K/O showed similar pathogenicity in mice to the KS07_WT, whereas KS07_N66S displayed enhanced virulence when compared to the other two viruses. KS07_WT exhibited more efficient replication in lungs and nasal shedding in infected pigs than the other two viruses. Pigs infected with the KS07_WT had higher pulmonary levels of granulocyte-macrophage colony-stimulating factor, IFN-γ, IL-6 and IL-8 at 3 and 5 days post-infection, as well as lower levels of IL-2, IL-4 and IL-12 at 1 day post-infection compared to those infected with the KS07_K/O. These results indicate that PB1-F2 modulates KS07 H1N1 virus replication, pathogenicity and innate immune responses in pigs and the single substitution at position 66 (N/S) in the PB1-F2 plays a critical role in virulence in mice. Taken together, our results provide new insights into the effects of PB1-F2 on the virulence of influenza virus in swine and support PB1-F2 as a virulence factor of influenza A virus in a strain- and host-dependent manner.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Henningson
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Jingjiao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Duff
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Yuekun
authors.initials: Y
authors.lastname: Lang
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Yonghai
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Present address: Department of Virology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.|Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Abdou
authors.initials: A
authors.lastname: Nagy
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Sunwoo
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Bawa
authors.affiliation: Innovation Team for Pathogen Ecology Research on Animal Influenza Virus, Department of Avian Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China.|Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Animal Science, Fujian Agriculture and Forestry University, Fuzhou, PR China.|Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Dingping
authors.initials: D
authors.lastname: Bai
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Richt
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ma
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000662:veterinary* / Q000821:virology; D013552:Swine / Q000276:immunology / Q000821:virology; D013553:Swine Diseases / Q000821:virology; D014764:Viral Proteins / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: C442816:PB1-F2 protein, Influenza A virus; D014764:Viral Proteins; D037521:Virulence Factors
keywords: PB1-F2; mouse and pig; pathogenicity; swine influenza H1N1 virus