title: Combination of PB2 271A and SR polymorphism at positions 590/591 is critical for viral replication and virulence of swine influenza virus in cultured cells and in vivo.
abstract: Triple reassortant swine influenza viruses (SIVs) and 2009 pandemic H1N1 (pH1N1) virus contain an avian-origin PB2 with 271A, 590S, 591R, and 627E. To evaluate the role of PB2 271A, 590S, and 591R in the replication and virulence of SIV, single (1930-TX98-PB2-271T)-, double (1930-TX98-PB2-590A591A)-, and triple (1930-TX98-PB2-271T590A591A)-mutated viruses were generated in the background of the H1N1 A/swine/Iowa/15/30 (1930) virus with an avian-origin PB2 from the triple-reassortant A/swine/Texas/4199-2/98 (TX98) virus, called the parental 1930-TX98-PB2. Compared to parental virus and single- and double-mutated viruses, the triple-mutated virus replicated less efficiently in cell cultures and was attenuated in mice. These results suggest that a combination of 271A with the 590/591 SR polymorphism is critical for pH1N1 and triple-reassortant SIVs for efficient replication and adaptation in mammals.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA. wma@vet.k-state.edu
authors.forename: Qinfang
authors.initials: Q
authors.lastname: Liu
authors.forename: Chuanling
authors.initials: C
authors.lastname: Qiao
authors.forename: Henju
authors.initials: H
authors.lastname: Marjuki
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Bawa
authors.forename: Jingqun
authors.initials: J
authors.lastname: Ma
authors.forename: Stephane
authors.initials: S
authors.lastname: Guillossou
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Richt
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ma
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D007251:Influenza, Human / Q000821:virology; D051379:Mice; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000662:veterinary* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D016865:Reassortant Viruses / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D013552:Swine; D013553:Swine Diseases / Q000401:mortality / Q000821:virology*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication
chemical_list: C057027:PB2 protein, Influenzavirus A; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
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