The HIV-1 envelope contains multiply overlapping (and redundant) mechanisms of humoral immune defence. These including glycan shielding, conformational masking, and immunodominant decoys with variable loops. Although explored extensively, many of these mechanisms are still only partially understood. We are using structure-based methods to define them further. In particular, we have investigated how the CD4-binding-site uses conformational masking to hide the conserved site of CD4 binding from most CD4-binding-site-directed antibodies. We have also investigated the functional conservation of the V3 loop of gp120, which is a principle site of neutralization for laboratory isolates, but appears to be occluded on primary isolates. Derivation of functional virus, with V3 truncated, provides proof-of-principle that other portions of the HIV-1 envelope can compensate for V3 function.
