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: 10170254
• 负责人: RICHARD J ROLLER
• 金额: $ 19.31万
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170254
• 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细胞系中，在微管组织中心（MTOC）周围形成了一个假定的细胞质病毒组装中心（cVAC）。人类巨细胞病毒（HCMV）是一种非神经侵入性的人类疱疹病毒，它在上皮细胞和成纤维细胞中形成视觉上明显不同的cVAC。HCMV组装的这一特征使其成为发现病毒组装中病毒包被蛋白功能以及病毒形态发生和输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，对HSV cVAC的研究将使该领域取得类似的快速进展，1)将为揭示HSV组装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力学和必需的病毒或宿主因子，2)将是发现HSV组装蛋白功能机制的丰富来源。3)将使我们能够比较HCMV和HSV之间的细胞质组装，这不仅提供了关于HSV同源物功能的见解，而且对其他疱疹病毒的组装也有意义。我们在此提议探索假设的HSV cVAC的组成，并测试关于微管网络、内吞作用和病毒被皮蛋白pUL51在其形成中的重要性的特定假设。