内吞体分选转运复合体 (ESCRT) 及其在包膜病毒出芽中的作用

Cellular ESCRT complex and its roles in enveloped viruses budding

摘要:

内吞体分选转运复合体 (Endosomal sorting complex required for transport，ESCRT) 主要识别泛素化修饰的膜蛋白，介导内吞小泡出芽和多泡体 (Multivesicular bodies，MVBs) 的形成。此外，以类似的拓扑方式，ESCRT也参与胞质分裂、自体吞噬、以及包膜病毒的出芽等过程。已有的研究表明，大量的反转录病毒和RNA病毒含有晚期结构域 (Late-domains)，该结构域与ESCRT组分相互作用，将ESCRT-Ⅲ和VPS4等募集在病毒组装与出芽区域，并利用ESCRT-Ⅲ使病毒粒子得以释放。最近，有研究发现，一些DNA包膜病毒、如乙肝病毒、疱疹病毒和杆状病毒等的出芽释放也依赖于宿主细胞ESCRT系统，但其机理尚需深入研究。

Abstract:

In eukaryotic cells, multivesicular bodies (MVBs) are required for trafficking of membrane proteins to lysosomes for selective destruction. The sorting of ubiquitylated membrane proteins into multivesicular bodies and the biogenesis of MVBs are mediated by the endosomal sorting complex required for transport (ESCRT). Topologically equivalent to the budding of intralumenal vesicles from the limiting membrane of the MVBs, the ESCRT complex is also involved in cytokinetic abscission, phagophore formation, and enveloped virus budding. Many retroviruses and RNA viruses encode “late-domain” motifs that are able to interact with the components of the ESCRT complex, and the interactions recruit ESCRT-III and VPS4 to the viral assembly and budding sites. Recently, few studies revealed that the ESCRT complex is also required for efficient egress of some DNA viruses, including Hepatitis B, Herpes simplex virus type-1, and Autographa californica multiple nucleopolyhedrovirus. Further examination of virus-ESCRT interactions should shed light on the detailed mechanism of virus assembly and budding.