Binding of gp120 to CD4 induces conformational changes that enable interaction with the CCR5 and CXCR4 coreceptors. Interaction with the coreceptors triggers additional changes, including extension of the gp41 FP and its insertion into the host cell membrane to form the extended, prehairpin intermediate and subsequent zipping up of the HR2 domains around the inner HR1 trimeric core to form a six-helix bundle. This brings together the FP and TMD and, therefore, the viral and host membranes, facilitating hemifusion, fusion, and pore formation. Abbreviations: C, conserved region; CT, cytoplasmic tail; FP, fusion peptide; HIV-1, human immunodeficiency virus type 1; HR, heptad repeat; MPER, membrane-proximal external region; SP, signal peptide; TMD, transmembrane domain; V, variable region. Figure adapted from images created with BioRender.com.