Inhibition of the TRAIL Death Receptor by CMV Reveals Its Importance in NK Cell-Mediated Antiviral Defense

Tnf-related apoptosis inducing ligand (trail) death receptors (dr) regulate apoptosis and inflammation,but their role in antiviral defense is poorly understood. cytomegaloviruses (cmv) encode many immune-modulatory genes that shape host immunity,and they utilize multiple strategies to target the tnf-family cytokines. here we show that the m166 open reading frame (orf) of mouse cmv (mcmv) is strictly required to inhibit expression of trail-dr in infected cells. an mcmv mutant lacking m166 expression (m166stop) is severely compromised for replication in vivo,most notably in the liver,and depleting natural killer (nk) cells,or infecting trail-dr−/− mice,restored mcmv-m166stop replication completely. these results highlight the critical importance for cmv to have evolved a strategy to inhibit trail-dr signaling to thwart nk-mediated defenses. © 2014 verma et al.