title: New virulence determinants contribute to the enhanced immune response and reduced virulence of an influenza A virus A/PR8/34 variant.
abstract: The identification of amino acid motifs responsible for increased virulence and/or transmission of influenza viruses is of enormous importance to predict pathogenicity of upcoming influenza strains. We phenotypically and genotypically compared 2 variants of influenza virus A/PR/8/34 with different passage histories. The analysis revealed differences in virulence due to an altered type I interferon (IFN) induction, as evidenced by experiments using IFNAR(-/-) mice. Interestingly, these differences were not due to altered functions of the well-known viral IFN antagonists NS1 or PB1-F2. Using reassortant viruses, we showed that differences in the polymerase proteins and nucleoprotein determined the altered virulence. In particular, changes in PB1 and PA contributed to an altered host type I IFN response, indicating IFN antagonistic properties of these proteins. Thus, PB1 and PA appear to harbor previously unknown virulence markers, which may prove helpful in assessing the risk potential of emerging influenza viruses.
authors: Institute of Molecular Virology, Center for Molecular Biology of Inflammation, University of Muenster, Germany.
authors: Swantje
authors: S
authors: Liedmann
authors: Eike R
authors: ER
authors: Hrincius
authors: Darisuren
authors: D
authors: Anhlan
authors: Jonathan A
authors: JA
authors: McCullers
authors: Stephan
authors: S
authors: Ludwig
authors: Christina
authors: C
authors: Ehrhardt
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D002645:Chickens; D016207:Cytokines / Q000032:analysis; D004285:Dogs; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D007370:Interferon Type I / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000737:chemistry / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D050794:STAT1 Transcription Factor; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014774:Virulence / Q000276:immunology
chemical_list: D016207:Cytokines; C085820:INS1 protein, influenza virus; D007370:Interferon Type I; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; D053633:Receptor, Interferon alpha-beta
keywords: influenza A virus; polymerase complex; type I interferon; virulence; virulence determinants