Figure 7.

A schematic illustration of an updated HIV-1 Env-mediated fusion model. The temporal sequence of Env conformational changes: (1) gp120 interacts with CD4; (2) conformational alteration in both molecules triggers binding to the cognate co-receptor; (3) FP exposure and membrane insertion; pre-hairpin intermediate formation; (4) gradual shedding of gp120 from the gp41 anchor further facilitates refolding of HR1 and HR2 of gp41, leading to (5) formation of NSC – an intermediate bundle structure of gp41 core; (6) mixing of the lipid outer leaflet; (7) recruitment of Env that acts in concert to promote and stabilize fusion pore; (8) full fusion (coalescence of both leaflets of apposing membranes) leading to content mixing.