title: Strain-dependent effects of PB1-F2 of triple-reassortant H3N2 influenza viruses in swine.
abstract: The PB1-F2 protein of the influenza A viruses (IAVs) can act as a virulence factor in mice. Its contribution to the virulence of IAV in swine, however, remains largely unexplored. In this study, we chose two genetically related H3N2 triple-reassortant IAVs to assess the impact of PB1-F2 in virus replication and virulence in pigs. Using reverse genetics, we disrupted the PB1-F2 ORF of A/swine/Wisconsin/14094/99 (H3N2) (Sw/99) and A/turkey/Ohio/313053/04 (H3N2) (Ty/04). Removing the PB1-F2 ORF led to increased expression of PB1-N40 in a strain-dependent manner. Ablation of the PB1-F2 ORF (or incorporation of the N66S mutation in the PB1-F2 ORF, Sw/99 N66S) affected the replication in porcine alveolar macrophages of only the Sw/99 KO (PB1-F2 knockout) and Sw/99 N66S variants. The Ty/04 KO strain showed decreased virus replication in swine respiratory explants, whereas no such effect was observed in Sw/99 KO, compared with the wild-type (WT) counterparts. In pigs, PB1-F2 did not affect virus shedding or viral load in the lungs for any of these strains. Upon necropsy, PB1-F2 had no effect on the lung pathology caused by Sw/99 variants. Interestingly, the Ty/04 KO-infected pigs showed significantly increased lung pathology at 3 days post-infection compared with pigs infected with the Ty/04 WT strain. In addition, the pulmonary levels of interleukin (IL)-6, IL-8 and gamma interferon were regulated differentially by the expression of PB1-F2. Taken together, these results indicate that PB1-F2 modulates virus replication, virulence and innate immune responses in pigs in a strain-dependent fashion.
authors: Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, USA.|Department of Veterinary Medicine, University of Maryland, College Park, MD, USA.
authors: Lindomar
authors: L
authors: Pena
authors: Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.
authors: Amy L
authors: AL
authors: Vincent
authors: Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.
authors: Crystal L
authors: CL
authors: Loving
authors: Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.
authors: Jamie N
authors: JN
authors: Henningson
authors: Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.
authors: Kelly M
authors: KM
authors: Lager
authors: Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, USA.|Department of Veterinary Medicine, University of Maryland, College Park, MD, USA.
authors: Weizhong
authors: W
authors: Li
authors: Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, USA.|Department of Veterinary Medicine, University of Maryland, College Park, MD, USA.
authors: Daniel R
authors: DR
authors: Perez
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004285:Dogs; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000821:virology; D016296:Mutagenesis / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary* / Q000821:virology*; D013552:Swine / Q000235:genetics / Q000276:immunology / Q000821:virology*; D019562:Viral Load / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology*; D014774:Virulence / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology; D017201:Virus Shedding / Q000235:genetics / Q000276:immunology
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; C442816:PB1-F2 protein, Influenza A virus; D014764:Viral Proteins; D037521:Virulence Factors; D007371:Interferon-gamma