title: Inhibition of interferon regulatory factor 3 activation by paramyxovirus V protein.
abstract: The V protein of Sendai virus (SeV) suppresses innate immunity, resulting in enhancement of viral growth in mouse lungs and viral pathogenicity. The innate immunity restricted by the V protein is induced through activation of interferon regulatory factor 3 (IRF3). The V protein has been shown to interact with melanoma differentiation-associated gene 5 (MDA5) and to inhibit beta interferon production. In the present study, we infected MDA5-knockout mice with V-deficient SeV and found that MDA5 was largely unrelated to the innate immunity that the V protein suppresses in vivo. We therefore investigated the target of the SeV V protein. We previously reported interaction of the V protein with IRF3. Here we extended the observation and showed that the V protein appeared to inhibit translocation of IRF3 into the nucleus. We also found that the V protein inhibited IRF3 activation when induced by a constitutive active form of IRF3. The V proteins of measles virus and Newcastle disease virus inhibited IRF3 transcriptional activation, as did the V protein of SeV, while the V proteins of mumps virus and Nipah virus did not, and inhibition by these proteins correlated with interaction of each V protein with IRF3. These results indicate that IRF3 is important as an alternative target of paramyxovirus V proteins.
authors.affiliation: Department of Virology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Irie
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kiyotani
authors.forename: Tomoki
authors.initials: T
authors.lastname: Igarashi
authors.forename: Asuka
authors.initials: A
authors.lastname: Yoshida
authors.forename: Takemasa
authors.initials: T
authors.lastname: Sakaguchi
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000276:immunology; D057131:Immune Evasion; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors* / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D029082:Sendai virus / Q000276:immunology / Q000472:pathogenicity*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000276:immunology / Q000378:metabolism; D037521:Virulence Factors / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*
chemical_list: C070065:36 kDa V protein, Newcastle disease virus; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D010750:Phosphoproteins; C539757:V protein, Nipah virus; C502891:V protein, Paramyxovirus; C111739:V protein, Sendai virus; C069181:V protein, measles virus; D014764:Viral Proteins; D015678:Viral Structural Proteins; D037521:Virulence Factors; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1