INHIBITION OF MITOCHONDRION-DEPENDENT APOPTOSIS BY HERPESVIRAL PROTEIN

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在病毒感染后，细胞经历凋亡作为对病毒复制的防御。反过来，病毒已经进化出复杂的机制来破坏凋亡过程。在这里，我们报告了一种新的病毒线粒体抗凋亡蛋白（vMAP）的鼠γ-疱疹病毒68（γ HV 68）与Bcl-2和VDAC 1在遗传上可分离的方式相互作用。vMAP的N-末端区域与Bcl-2相互作用，这种相互作用不仅显著增加Bcl-2向线粒体的募集，而且还增加其对仅BH 3促凋亡蛋白的亲合力，从而抑制Bax线粒体易位和活化。此外，vMAP的中心和C-末端疏水区与VDAC 1相互作用。因此，这些相互作用导致细胞色素c释放的有效抑制，从而全面抑制cytokine介导的细胞凋亡。最后，vMAP基因是正常细胞中γ HV 68裂解复制所必需的，但在线粒体凋亡缺陷细胞中不需要。艾滋病相关

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 gamma-herpesvirus 68 (gamma HV68) interacts with Bcl-2 and 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 proapoptotic 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 effective inhibition of cytochrome c release, leading to the comprehensive inhibition of mitochondrion-mediated apoptosis. Finally, vMAP gene was required for efficient gamma HV68 lytic replication in normal cells, but not in mitochondrial apoptosis-deficient cells. AIDS related.