| Human cytomegalovirus (HCMV) is a human pathogen that can cause severe diseases in immunocompromised individuals, and also is a leading cause for congenital infection, making it a major public health concern. Currently, there is no effective vaccine available and antiviral treatment is often associated with problems, like drug toxicity, and drug resistance. Intervention in the virus entry process during the replication cycle could serve as a useful therapeutic strategy. The overall aims of the research in this dissertation are to characterize the roles of HCMV two gH/gL glycoprotein complexes during virus entry and tropism, and to study the molecular basis for the regulation of the assembly of those two complexes. The work has revealed that gH/gL/gO complex promotes virus fusion into all cell types whereas gH/gL/UL128-131 complex provides a non-fusion but necessary function for virus entry into select cell types. Importantly, the work also demonstrated that different HCMV strains vary dramatically in the relative abundance of those two gH/gL complexes on the virion envelope, and that could have a fundamental impact on virus efficiency of entry. The regulation of the assembly of those two complexes is likely influenced by multiple viral factors. This work will help us better understand the molecular biology of how HCMV initiates infection of different cell types, and will aid in the development of antiviral strategies in the future. |
