Repression of EEF1D by KSHV RTA promotes viral lytic reactivation.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes lifelong latency in host cells but can periodically reactivate, a process that is essential for viral spread and disease development. The viral replication and transcription activator (RTA) serves as the master switch of this transition; however, the host factors that inhibit reactivation and the mechanisms by which RTA overcomes them remain incompletely defined. In this study, we identified the host protein eukaryotic translation elongation factor 1δ (EEF1D) as a previously unrecognized inhibitor of KSHV lytic replication. However, RTA inhibited EEF1D expression at both the protein and transcriptional levels. These findings expand the functional repertoire of RTA by revealing its ability to repress host gene transcription, providing new insights into viral persistence and pathogenesis.