Characterization of the herpes simplex virus cytoplasmic assembly center in neuronal cells

神经元细胞中单纯疱疹病毒细胞质组装中心的表征

• 批准号: 10038761
• 负责人: RICHARD J ROLLER
• 金额: $ 23.18万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-22 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10038761
• 关键词: Animal Model; Apical; Bacterial Artificial Chromosomes; Biology; Capsid; Capsid Proteins; Cell Culture Techniques; Cell Line; Cell Nucleus; Cell membrane; Cells; Cytomegalovirus; Cytoplasm; Data; Development; Docking; Dynein ATPase; Endocytosis; Epithelial Cells; Event; Fibroblasts; Glycoproteins; Herpesviridae; Herpesvirus 1; Human; Infection; Integration Host Factors; Kinesin; Maintenance; Membrane; Microtubules; Minus End of the Microtubule; Modeling; Morphogenesis; Motor; Mus; Mutagenesis; Nature; Neurons; Pathway interactions; Production; Proteins; Retrieval; Simplexvirus; Site; Source; Structure; System; Testing; Transmembrane Transport; Vaccines; Vesicle; Viral; Viral Genes; Viral Physiology; Viral Proteins; Virion; Virus Assembly; Virus Diseases; base; insight; novel; protein function; recruit

Recently, we have observed that, in at least one mouse and one human neuronal cell line, a putative cytoplasmic viral assembly center (cVAC) is formed around the microtubule organization center (MTOC). It is well-established that human cytomegalovirus (HCMV), a non-neuro-invasive human herpesvirus, forms a visually distinct cVAC in epithelial cells and fibroblasts. This feature of HCMV assembly has made it a rich source for discovery of functions of viral tegument proteins in viral assembly as well as host factors that are required for viral morphogenesis and egress. We believe that the study of an a HSV cVAC would allow similar rapid advances in the field by establishing a neuronal cell-based model that 1) would provide highly interpretable results for revealing the nature of the HSV assembly compartment, such as the dynamics of host membrane rearrangement during infection and essential viral or host factors required, 2) would be a rich source of discovery of mechanisms of HSV assembly protein function, 3) will allow us to compare cytoplasmic assembly between HCMV and HSV, which does not only provide insights regarding the functions of HSV homologs, but also has implications in the assembly of other herpesviruses. We propose here to explore the composition of the putative HSV cVAC and test specific hypotheses about the importance of microtubule networks, endocytosis, and the viral tegument protein pUL51 in its formation.

最近，我们观察到，在至少一种小鼠和一种人类神经元细胞系中，在微管组织中心（MTOC）周围形成了推定的细胞质病毒组装中心（cVAC）。众所周知，人类巨细胞病毒 (HCMV) 是一种非神经侵袭性人类疱疹病毒，在上皮细胞和成纤维细胞中形成视觉上不同的 cVAC。 HCMV 组装的这一特征使其成为发现病毒组装中病毒外皮蛋白的功能以及病毒形态发生和流出所需的宿主因子的丰富来源。我们相信，通过建立基于神经元细胞的模型，HSV cVAC 的研究将在该领域取得类似的快速进展，该模型 1）将为揭示 HSV 组装区室的性质提供高度可解释的结果，例如感染期间宿主膜重排的动态以及所需的基本病毒或宿主因子，2）将成为发现 HSV 组装蛋白功能机制的丰富来源，3）将使我们能够进行比较 HCMV 和 HSV 之间的细胞质组装，这不仅提供了有关 HSV 同源物功能的见解，而且对其他疱疹病毒的组装也有影响。我们在此建议探索假定的 HSV cVAC 的组成，并测试有关微管网络、内吞作用和病毒外皮蛋白 pUL51 在其形成中的重要性的具体假设。