title: Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA.
abstract: 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.
authors.affiliation: Centre National de la Recherche Scientifique, FRE2939, Institut Gustave Roussy, F-94805 Villejuif, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Poncet
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Pauleau
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Szabadkai
authors.forename: Angelo
authors.initials: A
authors.lastname: Vozza
authors.forename: Sebastian R
authors.initials: SR
authors.lastname: Scholz
authors.forename: Morgane
authors.initials: M
authors.lastname: Le Bras
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Brière
authors.forename: Abdelali
authors.initials: A
authors.lastname: Jalil
authors.forename: Ronan
authors.initials: R
authors.lastname: Le Moigne
authors.forename: Catherine
authors.initials: C
authors.lastname: Brenner
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hahn
authors.forename: Ilka
authors.initials: I
authors.lastname: Wittig
authors.forename: Hermann
authors.initials: H
authors.lastname: Schägger
authors.forename: Christophe
authors.initials: C
authors.lastname: Lemaire
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Bianchi
authors.forename: Sylvie
authors.initials: S
authors.lastname: Souquère
authors.forename: Gerard
authors.initials: G
authors.lastname: Pierron
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
authors.forename: Victor S
authors.initials: VS
authors.lastname: Goldmacher
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Palmieri
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D003588:Cytopathogenic Effect, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology* / Q000633:toxicity; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011108:Polymers / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology* / Q000633:toxicity; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D024101:Mitochondrial Proteins; D011108:Polymers; C420323:UL37 protein, Human herpesvirus 5; D014764:Viral Proteins; D051028:bcl-2-Associated X Protein; D000255:Adenosine Triphosphate