Human cytomegalovirus (HCMV) receptor-ligand interactions and viral entry excite cellular responses such as receptor tyrosine kinase and mitogen-activated protein kinase signaling, cytoskeletal rearrangement, and the induction of transcription factors, prostaglandins, and cytokines. Bi-phasic stimulation of these pathways, excepting interferon, facilitates productive viral infection and likely contributes to viral pathogenesis.