A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein

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A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein

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Title: A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein
Author: Feng, Pinghui; Liang, Chengyu; E, Xiaofei; Zhang, Weijun; Gravel, Robyn; Wu, Ting-ting; Sun, Ren; Usherwood, Edward; Shin, Young Cheol; Jung, Jae Ung

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Citation: Feng, Pinghui, Chengyu Liang, Young C. Shin, Xiaofei E., Weijun Zhang, Robyn Gravel, Ting-ting Wu, Ren Sun, Edward Usherwood, and Jae U. Jung. 2007. A novel inhibitory mechanism of mitochondrion-dependent apoptosis by a herpesviral protein. PLoS Pathogens 3(12): e174.
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Abstract: 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.
Published Version: doi:10.1371/journal.ppat.0030174
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134948/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:5691130

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