In vitro and in vivo characterization of Rh178, a rhesus cytomegalovirus-specific inhibitor of anitigen presentation

Cytomegalovirus (CMV) evades immune detection by inhibiting MHC-I antigen presentation. We identify Rh178, a Rhesus CMV protein that blocks MHC-I expression by interfering with translation of heavy chains prior to ER translocation. Rh178 localizes to the ER membrane with a cytosolic domain essential for this function. In vivo studies reveal that RhCMV superinfection in rhesus macaques requires multiple MHC-I inhibitors encoded in the Rh182–189 region, altering CD8+ T-cell immunodominance. These findings provide the first primate data on MHC-I immune evasion and inform strategies for CMV-based vaccine design.