Manipulation of Host Cell Death Pathways by Herpes Simplex Virus.
Manipulation of Host Cell Death Pathways by Herpes Simplex Virus.
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单纯疱疹病毒对宿主细胞死亡途径的操纵。
DOI：
10.1007/82_2020_196
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发表时间：
2023-01-01
影响因子：
--
通讯作者：
Han, Jiahuai
中科院分区：
文献类型：
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作者：
He, Sudan;Han, Jiahuai
单纯疱疹病毒（HSV）-1和HSV-2是普遍存在的人类病原体，其感染角化上皮表面并在外周神经系统的感觉神经元中建立终身潜伏感染。HSV-1引起口腔唇疱疹，HSV-2引起生殖器病变，其特征在于在初始感染部位复发。在多细胞生物中，细胞死亡通过清除病原体感染的细胞在宿主防御中起着关键作用。细胞凋亡和坏死是容易区分的细胞死亡类型。细胞凋亡是细胞程序性死亡的主要形式，取决于某些半胱氨酸蛋白酶家族的活性。坏死性凋亡是一种受调节的坏死形式，当半胱天冬酶活性受损时释放，需要通过与其他含RIP同型相互作用基序（RHIM）的蛋白质（如RIPK 1）相互作用激活受体相互作用蛋白（RIP）激酶3（RIPK 3）。为了确保在宿主中的终身感染，HSV执行复杂的分子策略以逃避病毒感染期间的宿主细胞死亡应答。HSV-1是一种充分表征的病原体，其编码有效的病毒抑制剂，所述病毒抑制剂以显著的物种特异性方式调节凋亡途径中的半胱天冬酶活化和坏死性凋亡途径中的RIPK 3活化。病毒UL 39编码的病毒蛋白ICP 6是病毒编码的核糖核苷酸还原酶的大亚基，在天然人类宿主中作为胱天蛋白酶-8和RHIM依赖性RIPK 3活性的抑制剂发挥作用。相比之下，ICP 6 RHIM介导的RIPK 3在非天然小鼠宿主中的募集驱动坏死性凋亡的直接激活。本章概述了HSV-1病毒蛋白和宿主细胞死亡途径之间分子相互作用的知识现状，并强调了HSV-1如何操纵细胞死亡信号以利于病毒繁殖。
Herpes simplex virus (HSV)-1 and HSV-2 are ubiquitous human pathogens that infect keratinized epithelial surfaces and establish lifelong latent infection in sensory neurons of the peripheral nervous system. HSV-1 causes oral cold sores, and HSV-2 causes genital lesions characterized by recurrence at the site of the initial infection. In multicellular organisms, cell death plays a pivotal role in host defense by eliminating pathogen-infected cells. Apoptosis and necrosis are readily distinguished types of cell death. Apoptosis, the main form of programmed cell death, depends on the activity of certain caspases, a family of cysteine proteases. Necroptosis, a regulated form of necrosis that is unleashed when caspase activity is compromised, requires the activation of receptor-interacting protein (RIP) kinase 3 (RIPK3) through its interaction with other RIP homotypic interaction motif (RHIM)-containing proteins such as RIPK1. To ensure lifelong infection in the host, HSV carries out sophisticated molecular strategies to evade host cell death responses during viral infection. HSV-1 is a well-characterized pathogen that encodes potent viral inhibitors that modulate both caspase activation in the apoptosis pathway and RIPK3 activation in the necroptosis pathway in a dramatic, species-specific fashion. The viral UL39-encoded viral protein ICP6, the large subunit of the virus-encoded ribonucleotide reductase, functions as a suppressor of both caspase-8 and RHIM-dependent RIPK3 activities in the natural human host. In contrast, ICP6 RHIM-mediated recruitment of RIPK3 in the nonnatural mouse host drives the direct activation of necroptosis. This chapter provides an overview of the current state of the knowledge on molecular interactions between HSV-1 viral proteins and host cell death pathways and highlights how HSV-1 manipulates cell death signals for the benefit of viral propagation.