Inhibition of interferon signaling by the Kaposi's sarcoma-associated herpesvirus full-length viral interferon regulatory factor 2 protein.
Interferon (IFN) signal transduction involves interferon regulatory factors (IRF). Kaposi's sarcoma-associated herpesvirus (KSHV) encodes four IRF homologues: viral IRF 1 (vIRF-1) to vIRF-4. Previous functional studies revealed that the first exon of vIRF-2 inhibited alpha/beta interferon (IFN-alpha/beta) signaling. We now show that full-length vIRF-2 protein, translated from two spliced exons, inhibited both IFN-alpha- and IFN-lambda-driven transactivation of a reporter promoter containing the interferon stimulated response element (ISRE). Transactivation of the ISRE promoter by IRF-1 was negatively regulated by vIRF-2 protein as well. Transactivation of a full-length IFN-beta reporter promoter by either IRF-3 or IRF-1, but not IRF-7, was also inhibited by vIRF-2 protein. Thus, vIRF-2 protein is an interferon induction antagonist that acts pleiotropically, presumably facilitating KSHV infection and dissemination in vivo.
Fuld
Suzanne
S
Lab22 Limited, Unit 184, The Science Park, Cambridge, United Kingdom.
Cunningham
Charles
C
Klucher
Kevin
K
Davison
Andrew J
AJ
Blackbourn
David J
DJ
D002460:Cell Line; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha; D014764:Viral Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D007372:Interferons