A Rhesus rhadinovirus viral interferon regulatory factor is virion-associated and inhibits the early interferon antiviral response

Two closely related gammaherpesviruses, Kaposi’s sarcoma-associated herpesvirus (KSHV) and rhesus macaque rhadinovirus (RRV), are unique in that they express viral homologues to cellular interferon (IFN) regulatory factors (IRFs), deemed viral IRFs (vIRFs). These vIRF proteins differentially regulate transcription and IFN signaling. The IFN response is an early host immune response dedicated to combating viral infection. Here, we demonstrate a strategy employed by RRV to ensure rapid inhibition of virus-induced type I IFN production. We show that vIRF ORF R6 impedes the IFN response within the first 6 h of poly(IC)-induced stimulation. We also found that RRV vIRF R6 interacts with transcriptional coactivator, CREB-binding protein (CBP), in the nucleus.