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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 i...

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Autores principales: Poncet, Delphine, Pauleau, Anne-Laure, Szabadkai, Gyorgy, Vozza, Angelo, Scholz, Sebastian R., Le Bras, Morgane, Brière, Jean-Jacques, Jalil, Abdelali, Le Moigne, Ronan, Brenner, Catherine, Hahn, Gabriele, Wittig, Ilka, Schägger, Hermann, Lemaire, Christophe, Bianchi, Katiuscia, Souquère, Sylvie, Pierron, Gerard, Rustin, Pierre, Goldmacher, Victor S., Rizzuto, Rosario, Palmieri, Ferdinando, Kroemer, Guido
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064390/
https://www.ncbi.nlm.nih.gov/pubmed/16982800
http://dx.doi.org/10.1083/jcb.200604069
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author Poncet, Delphine
Pauleau, Anne-Laure
Szabadkai, Gyorgy
Vozza, Angelo
Scholz, Sebastian R.
Le Bras, Morgane
Brière, Jean-Jacques
Jalil, Abdelali
Le Moigne, Ronan
Brenner, Catherine
Hahn, Gabriele
Wittig, Ilka
Schägger, Hermann
Lemaire, Christophe
Bianchi, Katiuscia
Souquère, Sylvie
Pierron, Gerard
Rustin, Pierre
Goldmacher, Victor S.
Rizzuto, Rosario
Palmieri, Ferdinando
Kroemer, Guido
author_facet Poncet, Delphine
Pauleau, Anne-Laure
Szabadkai, Gyorgy
Vozza, Angelo
Scholz, Sebastian R.
Le Bras, Morgane
Brière, Jean-Jacques
Jalil, Abdelali
Le Moigne, Ronan
Brenner, Catherine
Hahn, Gabriele
Wittig, Ilka
Schägger, Hermann
Lemaire, Christophe
Bianchi, Katiuscia
Souquère, Sylvie
Pierron, Gerard
Rustin, Pierre
Goldmacher, Victor S.
Rizzuto, Rosario
Palmieri, Ferdinando
Kroemer, Guido
author_sort Poncet, Delphine
collection PubMed
description 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.
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spelling pubmed-20643902007-11-29 Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA Poncet, Delphine Pauleau, Anne-Laure Szabadkai, Gyorgy Vozza, Angelo Scholz, Sebastian R. Le Bras, Morgane Brière, Jean-Jacques Jalil, Abdelali Le Moigne, Ronan Brenner, Catherine Hahn, Gabriele Wittig, Ilka Schägger, Hermann Lemaire, Christophe Bianchi, Katiuscia Souquère, Sylvie Pierron, Gerard Rustin, Pierre Goldmacher, Victor S. Rizzuto, Rosario Palmieri, Ferdinando Kroemer, Guido J Cell Biol Research Articles 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. The Rockefeller University Press 2006-09-25 /pmc/articles/PMC2064390/ /pubmed/16982800 http://dx.doi.org/10.1083/jcb.200604069 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Poncet, Delphine
Pauleau, Anne-Laure
Szabadkai, Gyorgy
Vozza, Angelo
Scholz, Sebastian R.
Le Bras, Morgane
Brière, Jean-Jacques
Jalil, Abdelali
Le Moigne, Ronan
Brenner, Catherine
Hahn, Gabriele
Wittig, Ilka
Schägger, Hermann
Lemaire, Christophe
Bianchi, Katiuscia
Souquère, Sylvie
Pierron, Gerard
Rustin, Pierre
Goldmacher, Victor S.
Rizzuto, Rosario
Palmieri, Ferdinando
Kroemer, Guido
Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA
title Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA
title_full Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA
title_fullStr Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA
title_full_unstemmed Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA
title_short Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA
title_sort cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vmia
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064390/
https://www.ncbi.nlm.nih.gov/pubmed/16982800
http://dx.doi.org/10.1083/jcb.200604069
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