Figure 1. Working model for human cytomegalovirus (HCMV) entry into cells. HCMV initially attaches in a tethering step to heparan sulfate proteoglycans (HSPGs) through
gM/gN and/or gB glycoproteins. In a stable docking step, gB interacts with the epidermal growth factor receptor (EGFR) on many HCMV-permissive cell types or with as yet
unidentified receptors in hematopoietic cells. Other interactions between the glycoproteins of the HCMV envelope and cellular integrins promote receptor clustering. At
least one of these interactions triggers fusion that leads to the internalization of virion components. Signal transduction events are initiated through EGFRs and/or integrins
and these events are hypothesized to prime and facilitate downstream steps in the virus lifecycle such as nuclear translocation of the capsid and efficient viral gene
expression. Toll-like receptors (TLRs) detect an HCMV-displayed pathogen-associated molecular pattern during the entry of the virus leading to distinct signaling events
and the activation of innate immunity.