title: Contribution of the interaction between the rabies virus P protein and I-kappa B kinase ϵ to the inhibition of type I IFN induction signalling.
abstract: The P protein of rabies virus (RABV) is known to interfere with the phosphorylation of the host IFN regulatory factor 3 (IRF-3) and to consequently inhibit type I IFN induction. Previous studies, however, have only tested P proteins from laboratory-adapted fixed virus strains, and to the best of our knowledge there is no report about the effect of P proteins from street RABV strains or other lyssaviruses on the IRF-3-mediated type I IFN induction system. In this study, we evaluated the inhibitory effect of P proteins from several RABV strains, including fixed and street virus strains and other lyssaviruses (Lagos bat, Mokola and Duvenhage viruses), on IRF-3 signalling. All P proteins tested inhibited retinoic acid-inducible gene-1 (RIG-I)- and TANK binding kinase 1 (TBK1)-mediated IRF-3-dependent IFN-β promoter activities. On the other hand, the P proteins from the RABV street strains 1088 and HCM-9, but not from fixed strains Nishigahara (Ni) and CVS-11 and other lyssaviruses tested, significantly inhibited I-kappa B kinase ϵ (IKKϵ)-inducible IRF-3-dependent IFN-β promoter activity. Importantly, we revealed that the P proteins from the 1088 and HCM-9 strains, but not from the remaining viruses, interacted with IKKϵ. By using expression plasmids encoding chimeric P proteins from the 1088 strain and Ni strain, we found that the C-terminal region of the P protein is important for the interaction with IKKϵ. These findings suggest that the P protein of RABV street strains may contribute to efficient evasion of host innate immunity.
authors.affiliation: Transboundary Animal Diseases Research Center, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Masatani
authors.affiliation: Transboundary Animal Diseases Research Center, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.|Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozawa
authors.affiliation: Research Promotion Institute, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.|Department of Microbiology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Ito
authors.affiliation: Transboundary Animal Diseases Research Center, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Horie
authors.affiliation: Transboundary Animal Diseases Research Center, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Matsuu
authors.affiliation: Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Okuya
authors.affiliation: Transboundary Animal Diseases Research Center, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.|Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsukiyama-Kohara
authors.affiliation: Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Department of Microbiology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishizono
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D057131:Immune Evasion; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors*; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D018832:Molecular Chaperones; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D011820:Rabies virus / Q000276:immunology* / Q000502:physiology*; D014158:Transcription, Genetic; D015678:Viral Structural Proteins / Q000378:metabolism*
chemical_list: D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D018832:Molecular Chaperones; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D015678:Viral Structural Proteins; D051550:I-kappa B Kinase