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
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