Single-molecule analysis of cell-virus binding interactions

Adhesion assays based on single molecule interactions are a useful option when discerning between avidity and affinity in complex systems. This is especially true for viral adhesion to living cells which typically involves a complex system of proteins working together to lead to productive infection. Here, we discuss assays that have been used to quantitatively study the adhesion of viral and cellular receptors including surface plasmon resonance, real time fusion assays involving viral fluorescent tags and single molecule force spectroscopy (SMFS). We highlight the advantages of SMFS over other methods, including its specificity, versatility and application to studying the adhesion of HIV-1 to human cells. We discuss how using SMFS with infectious virus and living cells allow us to distinguish the adhesion of HIV-1 surface protein, gp120, to its primary cellular receptor, CD4, from the adhesion of gp120 to its secondary co-receptor, CCR5.