Herpes simplex virus inhibits apoptosis through the action of two genes, Us5 and Us3

Apoptosis of virus-infected cells occurs either as a direct response to vir al infection or upon recognition of infection by the host immune response. Apoptosis reduces production of new virus from these cells, and therefore v iruses have evolved inhibitory mechanisms. We previously showed that labora tory strains of herpes simplex virus type I (HSV-1) protect infected cells from apoptosis induced by cytotoxic T lymphocytes or ethanol. We have now e valuated the ability of HSV-1 and HSV-2 laboratory and clinical isolates to inhibit apoptosis induced by anti-Fas antibody or UV irradiation and explo red the genetic basis for this inhibition. HSV-1 isolates inhibited apoptos is induced by UV or anti-Fas antibody. In contrast, HSV-2 clinical isolates failed to inhibit apoptosis induced by either stimulus, although the HSV-2 laboratory strain 333 had a partial inhibitory effect on UV-induced apopto sis. Inhibition of apoptosis by Hm was accompanied by marked reduction of c aspase-3 and caspase-8 activity. Deletion of the HSV-1 Us3 gene markedly re duced inhibition of W-induced apoptosis and partially abrogated inhibition of Pas-mediated apoptosis. Conversely, deletion of the HSV-1 Us5 gene marke dly reduced protection from Fas-mediated apoptosis and partially abrogated protection from UV. The Us11 and Us12 genes were not necessary for protecti on from apoptosis induced by either stimulus. The differences between HSV-1 and HSV-2 in the ability to inhibit apoptosis may be factors in the immuno biology of HSV infections.