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 and glycan shielding to hide the conserved site of CD4 binding from most CD4-binding-site-directed antibodies. We have also investigated how the envelope architecture provides for conformational mobility. These conformational layers in the HIV-1 gp120 inner domain regulate gp41 interactions and CD4-triggered conformational transitions.
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