title: Analysis of interaction of Sendai virus V protein and melanoma differentiation-associated gene 5.
abstract: Sendai virus (SeV), a pneumotropic virus of rodents, has an accessory protein, V, and the V protein has been shown to interact with MDA5, inhibiting IRF3 activation and interferon-β production. In the present study, interaction of the V protein with various IRF3-activating proteins including MDA5 was investigated in a co-immunoprecipitation assay. We also investigated interaction of mutant V proteins from SeVs of low pathogenicity with MDA5. The V protein interacted with at least retinoic acid inducible gene I, inhibitor of κB kinase epsilon and IRF3 other than MDA5. However, only MDA5 interacted with the V protein dependently on the C-terminal V unique (Vu) region, inhibiting IRF3 reporter activation. The Vu region has been shown to be important for viral pathogenicity. We thus focused on interaction of the V protein with MDA5. Point mutations in the Vu region destabilized the V protein or abolished the interaction with MDA5 when the V protein was stable. The V-R₃₂₀G protein was highly stable and interacted with MDA5, but did not inhibit activation of IRF3 induced by MDA5. Viral pathogenicity of SeV is related to the inhibitory effect of the V protein on MDA5, but is not always related to the binding of V protein with MDA5.
authors.affiliation: Department of Virology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: Takemasa
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Irie
authors.forename: Masaru
authors.initials: M
authors.lastname: Kuwayama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ueno
authors.forename: Asuka
authors.initials: A
authors.lastname: Yoshida
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kawabata
mesh_terms: D000818:Animals; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D015534:Trans-Activators / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D050505:Mutant Proteins; C502844:Rai1 protein, mouse; D015534:Trans-Activators; C111739:V protein, Sendai virus; D014764:Viral Proteins; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1