Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA

J Cell Biol. 2006 Sep 25;174(7):985-96. doi: 10.1083/jcb.200604069. Epub 2006 Sep 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis* / drug effects
  • Cytomegalovirus / genetics
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / metabolism*
  • Cytopathogenic Effect, Viral
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / pathology
  • Fibroblasts / virology
  • HeLa Cells
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / physiology*
  • Immediate-Early Proteins / toxicity
  • Mice
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • NIH 3T3 Cells
  • Oxidative Phosphorylation / drug effects
  • Polymers / metabolism
  • Viral Proteins / genetics
  • Viral Proteins / physiology*
  • Viral Proteins / toxicity
  • bcl-2-Associated X Protein / antagonists & inhibitors
  • bcl-2-Associated X Protein / genetics


  • Actins
  • Enzyme Inhibitors
  • Immediate-Early Proteins
  • Mitochondrial Proteins
  • Polymers
  • UL37 protein, Human herpesvirus 5
  • Viral Proteins
  • bcl-2-Associated X Protein
  • Adenosine Triphosphate