P34.04
Background: HIV-1 prevention through vaccination remains challenging due to the high mutation rate and variability amongst viral strains meaning that the identification of epitopes that elicit a truly broadly cross clade neutralizing virus is an immensely complex task. Identifying vaccine targets is further complicated by the presence of N-linked glycans on the surface of gp120 that protects the virion from recognition by the host immune system. Recently, however, broadly cross-neutralizing (BCN) antibodies have been identified that recognize specific glycans on the surface of gp120 and result in the neutralization of a broad panel of HIV viruses. Studies have identified that the glycans bound at either N332 or N334 in the C3 region at the base of the V3 loop are critical for susceptibility to, or evasion of neutralisation. The structural mechanism of this critical process is not yet fully understood.
Methods: Using the full gp120 structure, containing both the V1/V2 loops and V3 loop, we performed a molecular dynamics study to model the effect of the movement of glycosylation from 332 to 334 on both the ‘glycan shield’ and the underlying protein and, thus, on the susceptibility to neutralization.
Results: We have identified features of the glycan-glycan, as well as glycan-protein, interaction that may appear to play a role in the recognition of these epitopes by BCN antibodies as well as in the evasion of neutralization.
Conclusions: Our current research therefore contributes to the understanding of the role of N-linked glycosylation in the context of BCN antibodies and their associated epitopes.
