Understanding mechanisms of HIV-1 entry into cells

Abstract

Human immunodeficiency virus type 1 (HIV-1) attaches to cells by the stepwise interaction of its envelope glycoproteins (Env), which exist as trimers that stud the exterior of the virus particle, with cellular CD4 and a coreceptor, principally either of the chemokine receptors CCR5 or CXCR4. Virus entry into cells then proceeds via exposure of a viral fusion peptide, and fusion between the viral and cellular membranes. Adaptability in Env conformation is a hallmark of HIV-1, which permits the virus to escape the humoral immune response. HIV-1 may also harness this power of adaptability to alter its target cell tropism and develop resistance to CCR5 antagonist HIV-1 entry inhibitors. Our workhas shown that thismayoccur throughamore efficient interaction between the Env glycoproteins and cellular receptors, as well as by an altered (but not necessarily more efficient) mechanism of interaction. Understanding the complexity of these interactions is pivotal for elucidating the molecular determinants of HIV-1 pathogenesis.