A cytomegalavirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2

Human cytomegalovirus (CMV), a herpesvirus that causes congenital disease a nd opportunistic infections in immunocompromised individuals, encodes funct ions that facilitate efficient viral propagation by altering host cell beha vior. Here we show that CMV blocks apoptosis mediated by death receptors an d encodes a mitochondria-localized inhibitor of apoptosis, denoted vMIA, ca pable of suppressing apoptosis induced by diverse stimuli. vMIA, a product of the viral UL37 gene, inhibits Fas-mediated apoptosis at a point downstre am of caspase-8 activation and Bid cleavage but upstream of cytochrome c re lease, while residing in mitochondria and associating with adenine nucleoti de translocator. These functional properties resemble those ascribed to Bcl -2; however, the absence of sequence similarity to Bcl-2 or any other known cell death suppressors suggests that vMIA defines a previously undescribed class of anti-apoptotic proteins.