Journal
CELL HOST & MICROBE
Volume 21, Issue 6, Pages 777-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2017.05.003
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Funding
- NSF Graduate Research Fellowship [DGE-1256082]
- Cell and Molecular Biology Training Grant [T32GM007270]
- Molecular Biophysics Training Grant [T32GM0008268]
- NIH [R01GM102198, R01AI127893, DA039543, R01AI120961]
- Howard Hughes Medical Institute
- Simons Foundation
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Precisely defining how viral mutations affect HIV's sensitivity to antibodies is vital to develop and evaluate vaccines and antibody immunotherapeutics. Despite great effort, a full map of escape mutants has not been delineated for an anti-HIV antibody. We describe a massively parallel experimental approach to quantify how all single amino acid mutations to HIV Envelope (Env) affect neutralizing antibody sensitivity in the context of replication-competent virus. We apply this approach to PGT151, a broadly neutralizing antibody recognizing a combination of Env residues and glycans. We confirm sites previously defined by structural and functional studies and reveal additional sites of escape, such as positively charged mutations in the antibody-Env interface. Evaluating the effect of each amino acid at each site lends insight into biochemical mechanisms of escape throughout the epitope, highlighting roles for charge-charge repulsions. Thus, comprehensively mapping HIV antibody escape gives a quantitative, mutation-level view of Env evasion of neutralization.
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