The N-terminal V3 loop glycan modulates the interaction of clade A and B human immunodeficiency virus type 1 envelopes with CD4 and chemokine receptors

We investigated the underlying mechanism by which the highly conserved N-te rminal V3 loop glycan of gp120 conferred resistance to neutralization of hu man immunodeficiency virus type 1 (HIV-1). We find that the presence or abs ence of this V3 glycan on clade A and B viruses accorded various degrees of susceptibility to neutralization by antibodies to the CD4 binding site, CD 4-induced epitopes, and chemokine receptors. Our data suggest that this car bohydrate moiety on gp120 blocks access to the binding site for CD4 and mod ulates the chemokine receptor binding site of phenotypically diverse clade A and clade B isolates. Its presence also contributes to the masking of CD4 -induced epitopes on clade B envelopes. These findings reveal a common mech anism by which diverse HIV-1 isolates escape immune recognition. Furthermor e, the observation that conserved functional epitopes of HIV-1 are more exp osed on V3 glycan-deficient envelope glycoproteins provides a basis for exp loring the use of these envelopes as vaccine components.