Structural features of HIV envelope defined by antibody escape mutant analysis

Two neutralizing antibodies specific for the V3 sequence of HIV envelope were used to generate escape variants from the HTLVIIIB founder virus. The full gp120 sequence of each variant was then analyzed to identify mutations responsible for immune escape. As predicted, most escape variants harbored amino acid changes in the V3 crown sequence. However, one variant differed from its founder only within the conserved C2 region. These findings, when analyzed in conjunction with crystallographic data, suggest a new three-dimensional model for HIV envelope folding, in which the V3 loop extends across the CD4-binding face of gp120 to associate with discontinuous C2 residues. This envelope configuration may provide an effective immune defense mechanism for HIV, as the highly variable residues of the V3 loop may shield conserved amino acids pertinent to viral infection.