The U(S)3 protein kinase of herpes simplex virus 1 mediates the posttranslational modification of BAD and prevents BAD-induced programmed cell death in the absence of other viral proteins

Earlier studies have shown that the d120 mutant of herpes simplex virus 1, which lacks both copies of the alpha4 gene, induces apoptosis in all cell l ines tested. in some cell lines d120-induced apoptosis, manifested by the r elease of cytochrome c, activation of caspase 3, and fragmentation of cellu lar DNA, is blocked by the overexpression of Bcl-2. In these cells viral pr otein kinase U(S)3 delivered in trans blocks apoptosis induced by the mutan t virus at a premitochondrial stage. We report that the U(S)3 protein kinas e targets the pro-apoptotic BAD member of the Bcl-2 family. Specifically, t he U(S)3 protein kinase mediates a posttranslational modification of BAD an d blocks its cleavage, which is reported to activate apoptosis. Thus, U(S)3 protein kinase is the sole viral protein required to block activation of c aspase 3, prevent cleavage of poly(ADP-ribose) polymerase, and block fragme ntation of cellular DNA induced by BAD.