HIV enters cells by fusion at the cell surface, that results in a productive infection. The envelope (Env) protein of HIV mediates entry. Env is composed of a surface subunit, gp120, and a transmembrane subunit, gp41, which assemble as heterotrimers on the virion surface.The trimeric, surface gp120 protein (SU) on the virion engages CD4 on the host cell, inducing conformational changes that promote binding to select chemokine receptors CCR5 and CXCR4.
The sequential interplay between SU, CD4 and chemokine coreceptors prompts a conformational change in the transmembrane gp41. This coiled coil protein, assembled as a trimer on the virion membrane, springs open to project three peptide fusion domains that 'harpoon' the lipid bilayer of the target cell. A hairpin structure (also referred to as a "coiled coil bundle") is subsequently formed when the extracellular portion of gp41 collapses, and this hairpin formation promotes the fusion of virion and target cell membranes by bringing them into close proximity. Virion and target cell membrane fusion leads to the release of HIV viral cores into the cell interior.