Role of SUMOylation in Human Oncogenic Herpesvirus Infection

•Regulation of SUMO signaling in the EBV/KSHV latent infection.•Role of SUMOylation in reactivation of EBV/KSHV lytic replication.•Cross-talk between SUMO and Ubiquitin controls EBV/KSHV latent and lytic replication. Post-translational modification of target proteins by the Small Ubiquitin-like Modifier (SUMO) plays a critical role in regulation of many cellular processes including transcription, RNA processing, protein trafficking, DNA repair, and chromosome segregation, and is also often hijacked by viral infections. Epstein-Barr Virus (EBV) and Kaposi’s sarcoma-associated Herpesvirus (KSHV), two human oncogenic herpesviruses with a typical life cycle of latent and lytic replication, have been shown to be associated with many human cancers. In the past decade, intensive studies have investigated the interplay between tumor virus infection and SUMO-modification. In this review, we summarize the current knowledge as to how SUMOylation can regulate latent and lytic replication of EBV and KSHV, and the strategies by which these oncogenic herpesviruses usurp the SUMO pathways to establish a favorable microenvironment to promote host cell survival and proliferation in latency, and reactivate virion production during lytic replication, which are critical contributors to the development of EBV/KSHV-associated human malignancies.