title: An anti-interferon activity shared by paramyxovirus C proteins: inhibition of Toll-like receptor 7/9-dependent alpha interferon induction.
abstract: Paramyxovirus C protein targets the host interferon (IFN) system for virus immune evasion. To identify its unknown anti-IFN activity, we examined the effect of Sendai virus C protein on activation of the IFN-α promoter via various signaling pathways. This study uncovers a novel ability of C protein to block Toll-like receptor (TLR) 7- and TLR9-dependent IFN-α induction, which is specific to plasmacytoid dendritic cells. C protein interacts with a serine/threonine kinase IKKα and inhibits phosphorylation of IRF7. This anti-IFN activity of C protein is shared across genera of the Paramyxovirinae, and thus appears to play an important role in paramyxovirus immune evasion.
authors.affiliation: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Itoh
authors.affiliation: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. Electronic address: bing@belle.shiga-med.ac.jp.
authors.forename: Bin
authors.initials: B
authors.lastname: Gotoh
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010252:Paramyxoviridae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D015533:Transcriptional Activation; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; D051550:I-kappa B Kinase
keywords: C protein; ELISA; IFN; IFN-stimulated genes; IFN-β promoter stimulator-1; IKKα; IPS-1; IRAK1; IRF; ISGs; Interferon-α; IκB kinase alpha; MDA5; MeV; MyD88; N; NiV; Nipah virus; ORF; P; PAMPs; PIVs; PKR; Paramyxovirus; RIG-I; RIG-I-like receptors; RLRs; SDS; SeV; Sendai virus; TIR-domain-containing adapter-inducing interferon-β; TLR; TLR7; TRAF6; TRIF; Toll-like receptor; bPIV3; bovine PIV type 3; double stranded; ds; enzyme-linked immunosorbent assay; interferon; interferon regulatory factor; interleukin-1 receptor-associated kinase 1; mAb; measles virus; melanoma differentiation-associated gene 5; monoclonal antibody; myeloid differentiation factor 88; nucleocapsid protein; open reading frame; pAb; pDC; pDCs; parainfluenza viruses; pathogen-associated molecular patterns; phosphoprotein; plasmacytoid dendritic cells; polyclonal antibody; protein kinase R; retinoic acid-inducible gene-I; sodium dodecyl sulfate; tumor necrosis factor receptor-associated 6