We are interested in how human immunodeficiency virus type 1 (HIV-1) exploits cell-cell interactions to facilitate its spread throughout the immune system. We study adhesions that can form between infected and uninfected cells that are initiated by interactions between the viral glycoprotein, Env, and the cellular protein CD4. Our studies support a novel paradigm of the viral glycoprotein first acting as a cell-adhesion receptor, prior to serving its primary role as a viral entry protein. We have conducted live confocal imaging studies that have documented how virus assembly is coordinated with the formation of virological synapses. These have allowed us to track the transfer of virus particles into an internal compartment in the recipient cells. We have also learned that infection through virological synapses can resist neutralization by antibodies and results in the frequent simultaneous infection by multiple copies of HIV in the target cell. Our current studies are examining how virological synapses facilitate spread amongst cells in culture and in humanized mouse models. A better understanding of the immune cell interactions and migrations during HIV-1 infection by help to inform the development of better vaccines and drugs that can block cell-cell transmission.