The role of nonsense-mediated decay (NMD) in reactivation of the oncogenic herpesviruses EBV and KSHV

The oncogenic human herpesviruses Epstein-Barr virus (EBV) and Kaposis sarcoma-associated herpesvirus (KSHV) are the causative agents of multiple malignancies. A hallmark of herpesvirus infection is the biphasic life cycle consisting of latent and lytic infection. In this study, we identified that cellular nonsense-mediated decay (NMD), an evolutionarily conserved RNA degradation pathway, critically regulates the latent-to-lytic switch of EBV and KSHV infection. By performing RNA-IP sequencing (RIPseq) we identified EBV and KSHV viral transcripts associated with the key NMD factor UPF1 in latently and lytically EBV or KSHV-infected cells and found the viral transactivator transcripts to be the top hits associated with UPF1 in virus-infected cells.