HIV-1 Env is a primary target for antibodies elicited during infection. Although a small number of infected individuals elicit broadly neutralizing antibodies, the bulk of humoral response consists of antibodies that do not neutralize or do so with limited breadth and effect protection through Fc receptor-dependent processes, such as antibody-dependent cellular cytotoxicity (ADCC). We have used X-ray crystallography as the primary means for understanding Env mechanism of immune evasion, and in 2014 published the first full atomic-level structure of the pre-fusion closed HIV-1 Env trimer. This structure reveals gp41 conformational changes, location of sequence variation, and details of the glycan shield. We are trying to build on this atomic-level information to gain comprehensive insight into how HIV-1 Env evades neutralizing antibody. Of particular focus is an understanding of the HIV-1 glycan shield.
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