title: Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor-2 inhibits type 1 interferon signalling by targeting interferon-stimulated gene factor-3.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) encodes four viral interferon regulatory factors (vIRF-1-4). We investigated the mechanism and consequences of vIRF-2-mediated inhibition of interferon-response element signalling following type I interferon (IFN) induction. Western blot and electrophoretic mobility-shift assays identified the interferon-stimulated gene factor-3 (ISGF-3) components STAT1 and IRF-9 as the proximal targets of vIRF-2 activity. The biological significance of vIRF-2 inhibition of ISGF-3 was demonstrated by vIRF-2-mediated rescue of the replication of the IFN-sensitive virus encephalomyocarditis virus. This study provides both a mechanism and evidence for KSHV vIRF-2-mediated suppression of the consequences of type 1 IFN-induced signalling.
authors.affiliation: School of Cancer Sciences and Cancer Research UK Cancer Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Mutocheluh
authors.affiliation: School of Cancer Sciences and Cancer Research UK Cancer Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: L
authors.initials: L
authors.lastname: Hindle
authors.affiliation: School of Cancer Sciences and Cancer Research UK Cancer Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: C
authors.initials: C
authors.lastname: Aresté
authors.affiliation: School of Cancer Sciences and Cancer Research UK Cancer Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Chanas
authors.affiliation: School of Clinical and Experimental Medicine, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.|School of Cancer Sciences and Cancer Research UK Cancer Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Butler
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: K
authors.initials: K
authors.lastname: Lowry
authors.affiliation: Moorfields Lions Eye Bank, Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London EC1V 2PD, UK.
authors.forename: K
authors.initials: K
authors.lastname: Shah
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Evans
authors.affiliation: MRC Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, UK.|School of Cancer Sciences and Cancer Research UK Cancer Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Blackbourn
mesh_terms: D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D004686:Encephalomyocarditis virus / Q000254:growth & development / Q000276:immunology; D019288:Herpesvirus 8, Human / Q000276:immunology* / Q000472:pathogenicity*; D057131:Immune Evasion; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000037:antagonists & inhibitors*; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000276:immunology
chemical_list: C494227:IRF9 protein, human; D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014764:Viral Proteins; C413486:viral interferon regulatory factors