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，在至少一只小鼠和一个人神经元细胞系中，在微管组织中心（MTOC）周围形成了推定的细胞质病毒装配中心（CVAC）。众所周知的是，人类巨细胞病毒（HCMV）是一种非神经侵入性的人疱疹病毒，在上皮细胞和成纤维细胞中形成了视觉上不同的CVAC。 HCMV组装的这一特征使其成为发现病毒组装中病毒tegument蛋白功能的丰富来源，以及病毒形态发生和出口所需的宿主因子。我们认为，对A HSV CVAC的研究将通过建立基于神经元细胞的模型来允许在现场允许类似的快速进步，即1）将提供高度可解释的结果，以揭示HSV组装隔间的性质，例如，宿主膜膜重排的动力学在感染过程中和必需的病毒因子或允许的宿主允许的范围允许的源源于3的功能，将其概述为3的功能，概念3的源。 HCMV和HSV之间的细胞质组装不仅提供了有关HSV同源物功能的见解，而且还对其他疱疹病毒的组装有影响。我们在这里建议探索假定的HSV CVAC的组成，并检验有关微管网络，内吞作用和病毒tegument蛋白PUL51的重要性的特定假设。