The HIV-1 Entry Process: A Stoichiometric View

HIV-1 infection starts with fusion of the viral and the host cell membranes, a process mediated by the HIV-1 envelope glycoprotein trimer. The number of trimers required to complete membrane fusion, referred to as HIV-1 entry stoichiometry, remains under debate. A precise definition of HIV-1 entry stoichiometry is important as it reflects the efficacy of the viral entry process and steers the infectivity of HIV-1 virion populations. Initial estimates suggested a unanimous entry stoichiometry across HIV-1 strains while recent findings showed that HIV-1 strains can differ in entry stoichiometry. Here, we review current analyses of HIV-1 entry stoichiometry and point out future research directions to further define the interplay between entry stoichiometry, virus entry fitness, transmission, and susceptibility to antibody neutralization.

TrendsA refined understanding of the HIV entry stoichiometry emerges, indicating that most HIV-1 isolates require more than one envelope glycoprotein trimer for target cell entry.HIV-1 strains can differ in entry stoichiometry, reflecting the divergent potential of their envelope trimers to solicit energy required for the membrane fusion process.The HIV-1 entry stoichiometry is intimately linked with virus entry kinetics.The HIV-1 entry stoichiometry is a contributing factor of virus infectivity.The HIV-1 entry stoichiometry is an important parameter for the accurate determination of antibody numbers and concentrations required for virus neutralization.