title: Polymerase discordance in novel swine influenza H3N2v constellations is tolerated in swine but not human respiratory epithelial cells.
abstract: Swine-origin H3N2v, a variant of H3N2 influenza virus, is a concern for novel reassortment with circulating pandemic H1N1 influenza virus (H1N1pdm09) in swine because this can lead to the emergence of a novel pandemic virus. In this study, the reassortment prevalence of H3N2v with H1N1pdm09 was determined in swine cells. Reassortants evaluated showed that the H1N1pdm09 polymerase (PA) segment occurred within swine H3N2 with ∼ 80% frequency. The swine H3N2-human H1N1pdm09 PA reassortant (swH3N2-huPA) showed enhanced replication in swine cells, and was the dominant gene constellation. Ferrets infected with swH3N2-huPA had increased lung pathogenicity compared to parent viruses; however, swH3N2-huPA replication in normal human bronchoepithelial cells was attenuated - a feature linked to expression of IFN-β and IFN-λ genes in human but not swine cells. These findings indicate that emergence of novel H3N2v influenza constellations require more than changes in the viral polymerase complex to overcome barriers to cross-species transmission. Additionally, these findings reveal that while the ferret model is highly informative for influenza studies, slight differences in pathogenicity may not necessarily be indicative of human outcomes after infection.
authors.affiliation: Department of Infectious Diseases, Animal Health Research Center, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Powell
authors.affiliation: Department of Infectious Diseases, Animal Health Research Center, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dlugolenski
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Tamas
authors.initials: T
authors.lastname: Nagy
authors.affiliation: Department of Infectious Diseases, Animal Health Research Center, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Jon
authors.initials: J
authors.lastname: Gabbard
authors.affiliation: Department of Infectious Diseases, Animal Health Research Center, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Infectious Diseases, Animal Health Research Center, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Tompkins
authors.affiliation: Department of Infectious Diseases, Animal Health Research Center, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology*; D002454:Cell Differentiation; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000821:virology*; D005260:Female; D005289:Ferrets; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D016865:Reassortant Viruses / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D013045:Species Specificity; D013552:Swine; D014779:Virus Replication
chemical_list: D012321:DNA-Directed RNA Polymerases