Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
J Virol. 2020 Sep 15;94(19). doi: 10.1128/JVI.00900-20.
Herpes simplex virus (HSV) is a neuroinvasive virus that has been used as a model organism for studying common properties of all herpesviruses. HSV induces host organelle rearrangement and forms multiple, dispersed assembly compartments in epithelial cells, which complicates the study of HSV assembly. In this study, we show that HSV forms a visually distinct unitary cytoplasmic viral assembly center (cVAC) in both cancerous and primary neuronal cells that concentrates viral structural proteins and is a major site of capsid envelopment. The HSV cVAC also concentrates host membranes that are important for viral assembly, such as Golgi- and recycling endosome-derived membranes. Finally, we show that HSV cVAC formation and/or maintenance depends on an intact microtubule network and a viral tegument protein, pUL51. Our observations suggest that the neuronal cVAC is a uniquely useful model to study common herpesvirus assembly pathways and cell-specific pathways for membrane reorganization. Herpesvirus particles are complex and contain many different proteins that must come together in an organized and coordinated fashion. Many viruses solve this coordination problem by creating a specialized assembly factory in the host cell, and the formation of such factories provides a promising target for interfering with virus production. Herpes simplex virus 1 (HSV-1) infects several types of cells, including neurons, but has not previously been shown to form such an organized factory in the nonneuronal cells in which its assembly has been best studied. Here, we show that HSV-1 forms an organized assembly factory in neuronal cells, and we identify some of the viral and host cell factors that are important for its formation.
单纯疱疹病毒（HSV）是一种神经侵袭性病毒，已被用作研究所有疱疹病毒共同特性的模式生物。HSV 诱导宿主细胞器重排，并在上皮细胞中形成多个分散的装配隔室，这使得 HSV 装配的研究变得复杂。在这项研究中，我们表明 HSV 在癌细胞和原代神经元细胞中形成一个视觉上独特的单一细胞质病毒装配中心（cVAC），该中心浓缩病毒结构蛋白，是衣壳包被的主要部位。HSV cVAC 还浓缩了对病毒装配很重要的宿主膜，如高尔基体和再循环内体衍生的膜。最后，我们表明 HSV cVAC 的形成和/或维持依赖于完整的微管网络和一种病毒被膜蛋白 pUL51。我们的观察表明，神经元 cVAC 是研究常见疱疹病毒装配途径和细胞特异性膜重排途径的一个非常有用的模型。疱疹病毒颗粒结构复杂，包含许多不同的蛋白质，这些蛋白质必须以有组织和协调的方式聚集在一起。许多病毒通过在宿主细胞中创建一个专门的装配工厂来解决这个协调问题，而这种工厂的形成提供了一个有希望的干扰病毒产生的目标。单纯疱疹病毒 1（HSV-1）感染多种类型的细胞，包括神经元，但以前在其装配研究最好的非神经元细胞中尚未显示形成这种有组织的工厂。在这里，我们表明 HSV-1 在神经元细胞中形成一个有组织的装配工厂，并确定了一些对其形成重要的病毒和宿主细胞因素。
