INTRODUCTIONThe envelope (Env) glycoprotein of human immunodeficiency virus type-1 (HIV-1) is the virus attachment protein that interacts with the host-cell receptor CD4 and chemokine receptors CCR5 or CXCR4 to initiate infection (1). HIV-1 displays an average of 7–14 Env trimers per particle. However, this number varies among isolates (2). Env is synthesized as a gp160 precursor protein in the endoplasmic reticulum (ER), where signal peptide cleavage, folding, addition of high-mannose glycans, and trimerization in association with molecular chaperones take place (3–6). Once the nascent polypeptide attains its native folding state, the Env egresses from the ER and translocates to the Golgi apparatus (3, 7–13). In the Golgi, gp160 is cleaved by host furin-like proteases to generate a transmembrane gp41 subunit and a non-covalently associated surface gp120 subunit. Three gp120-gp41 heterodimers assemble to form the trimeric functional Env spikes that are then directed to the plasma membrane for incorporation into virions (3, 11–13). The gp120 subunit comprises five variable (V1–V5) and five conserved (C1–C5) regions. The V1V2 from each of the protomers join at the top to form the trimer apex, an immunogenic, structurally conserved region targeted by some of the most potent HIV-1 bNAbs (14–18). The gp41 subunit comprises the fusion machinery, mediating entry of the virus into the target cell by facilitating membrane fusion (19, 20). While trimeric Env is expected to be the most abundant form of Env present on virions, non-functional Env such as dimers, monomers, and gp41 stumps may also be present (21–23). These non-functional
Broadly neutralizing antibody epitopes on HIV-1 particles are exposed after virus interaction with host cells
