A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8activation

We have identified a human cytomegalovirus cell-death suppressor, denoted v ICA, encoded by the viral UL36 gene. vICA inhibits Fas-mediated apoptosis b y binding to the pro-domain of caspase-8 and preventing its activation. vIC A does not share significant sequence homology with FLIPs or other known su ppressors of apoptosis, suggesting that this protein represents a new class of cell-death suppressors. Notably, resistance to Fas-mediated apoptosis i s delayed in fibroblasts infected with viruses that encode mutant vICA, sug gesting that vICA suppresses death-receptor-induced cell death in the conte xt of viral infection. Although vICA is dispensable for viral replication i n vitro, the common targeting of caspase-8 activation by diverse herpesviru ses argues for an important role for this antiapoptotic mechanism in the pa thogenesis of viral infection in the host, most likely in avoiding immune c learance by cytotoxic: lymphocytes and natural killer cells.