Rhesus rhadinovirus vIRF R12 disrupts the PML-nuclear body via proteasome-dependent protein degradation pathway

Kaposi’s Sarcoma (KS), a common HIV-associated malignancy, is caused by KS-associated herpesvirus (KSHV). Due to limited models for KSHV infection, rhesus macaque rhadinovirus (RRV), a close homolog, serves as a surrogate. This study demonstrates that RRV infection downregulates promyelocytic leukemia protein (PML), an intrinsic immune regulator, primarily through viral interferon regulatory factor R12. The process is proteasome-dependent and involves nuclear aggregation followed by degradation. A Tet-ON/OFF system for R12 expression was developed for future studies. These findings highlight vIRFs as key immune modulators and potential therapeutic targets for KSHV-related disease.