Structure-function studies of the HIV-1 coreceptors

Ten seven-transmembrane-domain G protein-coupled receptors have been identified that are functional HIV-1, HIV-2 and SIV coreceptors. However, the specific structures these receptors have in common that enable them to mediate HIV entry are unknown. Structure-function analyses have revealed that the determinants of coreceptor activity are distinct for each coreceptor, coreceptor activity is dependent on multiple extracellular domains, and various envelope proteins may interact differently with the same coreceptor. G protein coupling and receptor internalization are not required for fusion and infection of established cell lines, or for inhibition of infection by chemokines. The structure-function studies have also helped determine the mechanism by which previously described small molecules inhibit HIV-1 entry. Finally, these studies have led to a hypothesis as to how coreceptor utilization evolves during the course of an infection.