Nectin-1: from receptor for herpes simplex virus to cell adhesion and innate immunity

Nectins form a family of cell adhesion molecules that also serve as receptors for numerous human viruses (incl. herpes simplex virus (HSV), measles virus, poliovirus). My work has focused on the role of nectin-1 in entry of HSV into cells.  This led to the current molecular model of activation of viral glycoproteins upon nectin-1 binding. Structural and functional data showed that the viral ligand (glycoprotein D) binds a functional site of nectin-1, thereby indicating that the virus will interfere with the natural functions of nectin-1, possibly to its own advantage. Therefore, more recently, I focused on understanding how HSV affects the natural roles of nectin-1 in cell-cell recognition through direct competition with ligands and induction of down-regulation. The recent discovery that nectins are involved in regulating the Natural Killer (NK) cell activation during the innate immune response also led us to investigate the role of nectin-1 as a ligand for NK cell receptors and adhesion molecules. This is leading us to develop a model of how HSV affect nectin-1 function to spread and potentially avoid the NK cell immune response.