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穿梭细胞质:α疱疹病毒基因组向细胞核的运输。

Navigating the Cytoplasm: Delivery of the Alphaherpesvirus Genome to the Nucleus.

机构信息

Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

出版信息

Curr Issues Mol Biol. 2021;41:171-220. doi: 10.21775/cimb.041.171. Epub 2020 Aug 18.

DOI:10.21775/cimb.041.171
PMID:32807747
Abstract

Herpesviruses virions are large and complex structures that deliver their genetic content to nuclei upon entering cells. This property is not unusual as many other viruses including the adenoviruses, orthomyxoviruses, papillomaviruses, polyomaviruses, and retroviruses, do likewise. However, the means by which viruses in the subfamily accomplish this fundamental stage of the infectious cycle is tied to their defining ability to efficiently invade the nervous system. Fusion of the viral envelope with a cell membrane results in the deposition of the capsid, along with an assortment of tegument proteins, into the cytosol. Establishment of infection requires that the capsid traverse the cytosol, dock at a nuclear pore, and inject its genome into the nucleoplasm. Accumulating evidence indicates that the capsid is not the effector of this delivery process, but is instead shepherded by tegument proteins that remain capsid bound. At the same time, tegument proteins that are released from the capsid upon entry act to increase the susceptibility of the cell to the ensuing infection. Mucosal epithelial cells and neurons are both susceptible to alphaherpesvirus infection and, together, provide the niche to which these viruses have adapted. Although much has been revealed about the functions of expressed tegument proteins during the late stages of assembly and egress, this review will specifically address the roles of tegument proteins brought into the cell with the incoming virion, and our current understanding of alphaherpesvirus genome delivery to nuclei.

摘要

疱疹病毒病毒粒子是大型且复杂的结构,进入细胞后将其遗传物质递送至细胞核。这种特性并不罕见,因为许多其他病毒,包括腺病毒、正粘病毒、乳头瘤病毒、多瘤病毒和逆转录病毒,也是如此。然而,亚科病毒完成感染周期这一基本阶段的方式与它们高效入侵神经系统的能力有关。病毒包膜与细胞膜融合导致衣壳以及一系列包膜蛋白沉积到细胞质中。感染的建立要求衣壳穿过细胞质,在核孔处停靠,并将其基因组注入核质。越来越多的证据表明,衣壳不是这种递呈过程的效应物,而是由仍然与衣壳结合的包膜蛋白引导。同时,在进入细胞时从衣壳释放的包膜蛋白会增加细胞对随后感染的易感性。黏膜上皮细胞和神经元都容易受到α疱疹病毒感染,两者共同为这些病毒提供了适应的小生境。尽管在晚期组装和出芽过程中已经揭示了许多表达的包膜蛋白的功能,但本综述将特别关注与进入细胞的病毒粒子一起带入的包膜蛋白的作用,以及我们对α疱疹病毒基因组递送至细胞核的当前理解。

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