Rhesus macaque rhadinovirus-associated disease

•RRV-associated disease.•RRV genome is highly similar to Kaposi sarcoma-associated herpesvirus genome.•RRV encodes similar open reading frames as KSHV that are postulated to be associated with disease.•Recombinant RRV clone is pathogenic and can be manipulated to interrogate viral ORFs. Rhesus macaque rhadinovirus (RRV) is a gamma-2 herpesvirus that naturally infects rhesus macaque (RM) monkeys and is closely related to human herpesvirus-8 (HHV-8)/Kaposi's sarcoma-associated herpesvirus (KSHV). Infection of immunodeficient RM induces disease in infected RM that resembles KSHV-associated pathologies. Importantly, RRV possesses homologues of KSHV ORFs that are postulated to play a role in disease development. As such, RRV has emerged as a prominent in vivo model system for examining mechanisms of infection and disease of these pathogenic herpesviruses, and has provided unique insight into how these viruses cause disease.