Department of Biochemistry and Molecular Biology, Institut de Biotecnologia i Biomedicina, Universitat de València, 46100, Burjassot, Spain.
Department of Molecular and Cell Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Campus Universidad Autónoma, 28049, Madrid, Spain.
Nat Commun. 2020 Nov 27;11(1):6056. doi: 10.1038/s41467-020-19881-9.
Viral control of programmed cell death relies in part on the expression of viral analogs of the B-cell lymphoma 2 (Bcl2) protein known as viral Bcl2s (vBcl2s). vBcl2s control apoptosis by interacting with host pro- and anti-apoptotic members of the Bcl2 family. Here, we show that the carboxyl-terminal hydrophobic region of herpesviral and poxviral vBcl2s can operate as transmembrane domains (TMDs) and participate in their homo-oligomerization. Additionally, we show that the viral TMDs mediate interactions with cellular pro- and anti-apoptotic Bcl2 TMDs within the membrane. Furthermore, these intra-membrane interactions among viral and cellular proteins are necessary to control cell death upon an apoptotic stimulus. Therefore, their inhibition represents a new potential therapy against viral infections, which are characterized by short- and long-term deregulation of programmed cell death.
病毒对细胞程序性死亡的调控部分依赖于病毒 B 细胞淋巴瘤 2（Bcl2）蛋白类似物（即病毒 Bcl2 蛋白，vBcl2）的表达。vBcl2 通过与宿主细胞 Bcl2 家族中的促凋亡和抗凋亡成员相互作用来控制细胞凋亡。在此，我们发现疱疹病毒和痘病毒 vBcl2 的羧基末端疏水区可充当跨膜结构域（TMD）并参与同源寡聚化。此外，我们还发现病毒 TMD 介导了与膜内细胞促凋亡和抗凋亡 Bcl2 TMD 的相互作用。此外，在凋亡刺激下，这些病毒和细胞蛋白之间的膜内相互作用对于控制细胞死亡是必需的。因此，抑制这些相互作用可能是一种针对以细胞程序性死亡的短期和长期失调为特征的病毒感染的新的潜在治疗方法。
