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

点击翻译按钮获取中文摘要

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.