NMR studies of V3 peptide complexes with antibodies suggest a mechanism for HIV-1 co-receptor selectivity

The third variable region (V3) of the HIV-1 envelope glycoprotein gp120 is involved in gp120 binding to the chemokine receptors CCR5 and CXCR4, which serve as co-receptors in HIV-1 infection. The sequence of V3 determines whether the virus binds to CCR5 and infects predominantly macrophages (R5 virus) or to CXCR4 and infects mostly T-cells (X4 virus). This review summarizes structural information for V3 peptides in complex with HIV-1 neutralizing antibodies. Nuclear magnetic resonance studies of the V3 peptides led to the proposal of a mechanism for co-receptor selectivity. Experiments to further explore this mechanism and potential applications of V3 structural information are discussed.