Abstract
Human cytomegalovirus (HCMV) entry into host cells is a complex process involving interactions between an array of viral glycoproteins with multiple host cell surface receptors. A significant amount of research has been devoted toward identifying these glycoprotein and cellular receptor interactions as the broad cellular tropism of HCMV suggests a highly regulated yet adaptable process that controls viral binding and penetration. However, deciphering the initial binding and cellular receptor activation events by viral glycoproteins remains challenging. The relatively low abundance of receptors and/or interactions with glycoproteins during viral entry, the hydrophobicity of membrane receptors, and the rapid degradation and recycling of activated receptors have complicated the analysis of HCMV entry and the cellular signaling pathways initiated by HCMV engagement to the host membrane. Here, we describe the different methodologies used in our laboratory and others to analyze the interactions between HCMV glycoproteins and host cellular receptors during the entry stage of the viral life cycle.