The envelope glycoprotein of HIV-1 gp160 (Env) is synthesized in the rough endoplasmic reticulum and subjected to extensive N glycosylation, resulting in high-mannose chains linked to Asn residues at either the Asn-X-Ser or the Asn-X-Thr glycosylation site. gp160 matures by enzymatic cleavage through the host protease furin before anchoring at the membrane surface, in two subunits associated by noncovalent interactions: the surface gp120 (SU) and the transmembrane (TM) gp41. gp120 represents the external part of the envelope glycoprotein and is involved in the early steps of viral infection of target cells. It consists of conserved (C) and variable (V) protein domains which, when folded, comprise an inner domain, an outer domain, and a bridging sheet. One of the viral defense mechanisms evolved against antibody neutralization is the masking of key regions on SU with glycans. In this respect, 20 to 24 N-glycosylation sites are present on gp120.