Center for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Curr Issues Mol Biol. 2021;42:551-604. doi: 10.21775/cimb.042.551. Epub 2021 Feb 24.
Alphaherpesvirus tegument assembly, secondary envelopment, and exocytosis processes are understood in broad strokes, but many of the individual steps in this pathway, and their molecular and cell biological details, remain unclear. Viral tegument and membrane proteins form an extensive and robust protein interaction network, such that essentially any structural protein can be deleted, yet particles are still assembled, enveloped, and released from infected cells. We conceptually divide the tegument proteins into three groups: conserved inner and outer teguments that participate in nucleocapsid and membrane contacts, respectively; and 'middle' tegument proteins, consisting of some of the most abundant tegument proteins that serve as central hubs in the protein interaction network, yet which are unique to the alphaherpesviruses. We then discuss secondary envelopment, reviewing the tegument-membrane contacts and cellular factors that drive this process. We place this viral process in the context of cell biological processes, including the endocytic pathway, ESCRT machinery, autophagy, secretory pathway, intracellular transport, and exocytosis mechanisms. Finally, we speculate about potential relationships between cellular defenses against oligomerizing or aggregating membrane proteins and the envelopment and egress of viruses.
α疱疹病毒的被膜组装、次包膜包裹和胞吐过程在很大程度上是已知的，但该途径的许多个别步骤及其分子和细胞生物学细节仍不清楚。病毒的被膜和膜蛋白形成了一个广泛而强大的蛋白质相互作用网络，因此几乎任何结构蛋白都可以被删除，但仍然可以组装、包裹和从感染细胞中释放病毒颗粒。我们从概念上将被膜蛋白分为三组：分别参与核衣壳和膜接触的保守的内被膜和外被膜；以及“中间”被膜蛋白，它们由一些最丰富的被膜蛋白组成，这些蛋白在蛋白质相互作用网络中充当中心枢纽，但它们是α疱疹病毒所特有的。然后，我们讨论了次包膜包裹，回顾了驱动该过程的被膜-膜接触和细胞因子。我们将这个病毒过程置于细胞生物学过程的背景下，包括内吞途径、ESCRT 机制、自噬、分泌途径、细胞内运输和胞吐机制。最后，我们推测了细胞对聚集或聚集膜蛋白的防御与病毒的包膜和出芽之间的潜在关系。
