HIV: cell binding and entry

Abstract

The first step of the human immunodeficiency virus (HIV) replication cycle—binding and entry into the host cell—plays a major role in determining viral tropism and the ability of HIV to degrade the human immune system. HIV uses a complex series of steps to deliver its genome into the host cell cytoplasm while simultaneously evading the host immune response. To infect cells, the HIV protein envelope (Env) binds to the primary cellular recep-tor CD4 and then to a cellular coreceptor. This sequential binding triggers fusion of the viral and host cellmembranes, initiating infection. Revealing themechanismofHIVentry has pro-found implications for viral tropism, transmission, pathogenesis, and therapeutic interven-tion. Here, we provide an overview into the mechanism of HIV entry, provide historical context to key discoveries, discuss recent advances, and speculate on future directions in the field. HIV ENTRY FUNDAMENTALS HIVentry, the first phase of the viral replica-tion cycle, begins with the adhesion of virus to the host cell and ends with the fusion of the cell and viralmembranes with subsequen