2 research outputs found
Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA.
Replication of human cytomegalovirus (CMV) requires the expression of the viral
mitochondria-localized inhibitor of apoptosis (vMIA). vMIA inhibits apoptosis by
recruiting Bax to mitochondria, resulting in its neutralization. We show that
vMIA decreases cell size, reduces actin polymerization, and induces cell
rounding. As compared with vMIA-expressing CMV, vMIA-deficient CMV, which
replicates in fibroblasts expressing the adenoviral apoptosis suppressor E1B19K,
induces less cytopathic effects. These vMIA effects can be separated from its
cell death-inhibitory function because vMIA modulates cellular morphology in
Bax-deficient cells. Expression of vMIA coincided with a reduction in the
cellular adenosine triphosphate (ATP) level. vMIA selectively inhibited one
component of the ATP synthasome, namely, the mitochondrial phosphate carrier.
Exposure of cells to inhibitors of oxidative phosphorylation produced similar
effects, such as an ATP level reduced by 30%, smaller cell size, and deficient
actin polymerization. Similarly, knockdown of the phosphate carrier reduced cell
size. Our data suggest that the cytopathic effect of CMV can be explained by vMIA
effects on mitochondrial bioenergetics