Replication efficiencies of human cytomegalovirus-infected epithelial cells are dependent on source of virus production.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause serious disease under conditions of immunodeficiency and upon congenital infection. HCMV replicates in diverse cell types throughout the human body with tropism influenced by the source of the virus. Here, we investigated the contribution of viral sources to the kinetics of HCMV replication in epithelial cells using both experimental and mechanistic computational modeling approaches. These studies reveal that HCMV produced from epithelial cells exhibits a higher efficiency of replication despite similar viral DNA synthesis kinetics between viral sources. These differences likely involve a propensity of epithelial-derived virus to induce syncytia versus fibroblast-derived virus, and an accompanying higher synthesis rate of a late virion protein ultimately resulting in production of more extracellular infectious virus.