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A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein
Upon viral infection, cells undergo apoptosis as a defense against viral replication. Viruses, in turn, have evolved elaborate mechanisms to subvert apoptotic processes. Here, we report that a novel viral mitochondrial anti-apoptotic protein (vMAP) of murine γ-herpesvirus 68 (γHV-68) interacts with...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134948/ https://www.ncbi.nlm.nih.gov/pubmed/18069888 http://dx.doi.org/10.1371/journal.ppat.0030174 |
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author | Feng, Pinghui Liang, Chengyu Shin, Young C E, Xiaofei Zhang, Weijun Gravel, Robyn Wu, Ting-ting Sun, Ren Usherwood, Edward Jung, Jae U |
author_facet | Feng, Pinghui Liang, Chengyu Shin, Young C E, Xiaofei Zhang, Weijun Gravel, Robyn Wu, Ting-ting Sun, Ren Usherwood, Edward Jung, Jae U |
author_sort | Feng, Pinghui |
collection | PubMed |
description | Upon viral infection, cells undergo apoptosis as a defense against viral replication. Viruses, in turn, have evolved elaborate mechanisms to subvert apoptotic processes. Here, we report that a novel viral mitochondrial anti-apoptotic protein (vMAP) of murine γ-herpesvirus 68 (γHV-68) interacts with Bcl-2 and voltage-dependent anion channel 1 (VDAC1) in a genetically separable manner. The N-terminal region of vMAP interacted with Bcl-2, and this interaction markedly increased not only Bcl-2 recruitment to mitochondria but also its avidity for BH3-only pro-apoptotic proteins, thereby suppressing Bax mitochondrial translocation and activation. In addition, the central and C-terminal hydrophobic regions of vMAP interacted with VDAC1. Consequently, these interactions resulted in the effective inhibition of cytochrome c release, leading to the comprehensive inhibition of mitochondrion-mediated apoptosis. Finally, vMAP gene was required for efficient γHV-68 lytic replication in normal cells, but not in mitochondrial apoptosis-deficient cells. These results demonstrate that γHV-68 vMAP independently targets two important regulators of mitochondrial apoptosis-mediated intracellular innate immunity, allowing efficient viral lytic replication. |
format | Text |
id | pubmed-2134948 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-21349482007-12-27 A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein Feng, Pinghui Liang, Chengyu Shin, Young C E, Xiaofei Zhang, Weijun Gravel, Robyn Wu, Ting-ting Sun, Ren Usherwood, Edward Jung, Jae U PLoS Pathog Research Article Upon viral infection, cells undergo apoptosis as a defense against viral replication. Viruses, in turn, have evolved elaborate mechanisms to subvert apoptotic processes. Here, we report that a novel viral mitochondrial anti-apoptotic protein (vMAP) of murine γ-herpesvirus 68 (γHV-68) interacts with Bcl-2 and voltage-dependent anion channel 1 (VDAC1) in a genetically separable manner. The N-terminal region of vMAP interacted with Bcl-2, and this interaction markedly increased not only Bcl-2 recruitment to mitochondria but also its avidity for BH3-only pro-apoptotic proteins, thereby suppressing Bax mitochondrial translocation and activation. In addition, the central and C-terminal hydrophobic regions of vMAP interacted with VDAC1. Consequently, these interactions resulted in the effective inhibition of cytochrome c release, leading to the comprehensive inhibition of mitochondrion-mediated apoptosis. Finally, vMAP gene was required for efficient γHV-68 lytic replication in normal cells, but not in mitochondrial apoptosis-deficient cells. These results demonstrate that γHV-68 vMAP independently targets two important regulators of mitochondrial apoptosis-mediated intracellular innate immunity, allowing efficient viral lytic replication. Public Library of Science 2007-12 2007-12-07 /pmc/articles/PMC2134948/ /pubmed/18069888 http://dx.doi.org/10.1371/journal.ppat.0030174 Text en © 2007 Feng et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Feng, Pinghui Liang, Chengyu Shin, Young C E, Xiaofei Zhang, Weijun Gravel, Robyn Wu, Ting-ting Sun, Ren Usherwood, Edward Jung, Jae U A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein |
title | A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein |
title_full | A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein |
title_fullStr | A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein |
title_full_unstemmed | A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein |
title_short | A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein |
title_sort | novel inhibitory mechanism of mitochondrion-dependent apoptosis by a herpesviral protein |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134948/ https://www.ncbi.nlm.nih.gov/pubmed/18069888 http://dx.doi.org/10.1371/journal.ppat.0030174 |
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