人巨细胞病毒（HCMV）感染是引起出生缺陷的主要病因，也是骨髓移植失败的最常见病因。HCMV结构复杂，迄今复制机制未完全阐明。我们前期发现宿主因子WDR5参与衣壳出核过程。进一步预实验发现：HCMV感染过程中特异性地挟持WDR5并聚集于病毒的装配中心，而其他DNA病毒（单纯疱疹病毒I型、水痘带状疱疹病毒、腺病毒和杆状病毒）感染无此现象；在病毒包装过程中WDR5可能被包装入病毒粒子。HCMV如何挟持WDR5进而调控病毒复制有待阐明。本项目将通过质谱分析筛选调控WDR5的病毒蛋白，经免疫共沉淀证实其相互作用；进一步通过构建重组突变病毒鉴定调控WDR5的病毒因子；通过敲降WDR5的表达，明确WDR5对病毒的装配中心（vAC）形成以及病毒粒子装配的影响，阐明HCMV挟持WDR5至vAC影响病毒包装的分子机制。本项目将为揭示HCMV利用宿主因子完成自身复制提供新的知识，为干预HCMV感染提供新靶标。

Congenital human cytomegalovirus (HCMV) infection is the leading cause of birth defects in children, and HCMV infection is also the most common cause of failure in patients following hematopoietic stem cell transplantation. The HCMV structure is sophisticated and the replication mechanism has not been fully clarified so far. We have previously found that the host factor WDR5 regulates HCMV replication and participates in capsids nuclear egress. The preliminary experiment of this project showed that HCMV specifically hijacked WDR5 to the virus assembly center (vAC) during its infection. Other DNA viruses (e.g. herpes simplex virus type I, varicella zoster virus, adenovirus and baculovirus) have no such phenomenon. What’s more, WDR5 may be packaged into virus particles during virus packaging. How HCMV regulates WDR5 and controls virus replication remains to be clarified. In order to solve this, we will screen the viral factors that regulate WDR5 via mass spectrometry and validate by co-immunoprecipitation and mutant recombinant viruses. On the other hand, WDR5 will be knocked down to clarify the impact of WDR5 on the formation of vAC and the assembly of viral particles, and further illuminate the molecular mechanism of HCMV to affect its own packaging by hijacking WDR5 to vAC. This project will provide new insights into HCMV's use of host factors to complete its own life cycle, and may provide candidate target molecules for the development of new methods to prevent and treat HCMV infections.