HIV-1 gp41: mediator of fusion and target for inhibition.

The bipartite envelope glycoprotein (Env) of the human immunodeficiency virus type 1 (HIV-1) performs two essential functions for initiating virus infection. The gp120 surface subunit of Env binds cell receptors to attach virus to target cells and regulate viral entry. The gp41 transmembrane subunit fuses host-cell and viral membranes to deliver the viral core into the cell cytoplasm. The two subunits derive from a polyprotein precursor, gp160. Cleavage of gp160 in the biosynthetic pathway creates mature Env consisting of the noncovalently-associated gp120/gp41 that is primed for viral entry. While performing distinct operations in HIV entry, the activities of the gp120 and gp41 subunits must be highly coordinated in order to lead to successful infection. This review highlights structure-function relationships in Env, with a focus on the heptad-repeat regions in the ectodomain of gp41. The mechanism of Env-mediated membrane fusion and ways to interfere with this process using inhibitors and antibodies that target gp41 are discussed.