Comprehensive Mapping of HIV-1 Escape from a Broadly Neutralizing Antibody.


Abstract

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.

Submission Details

ID: 58iNkMvc

Submitter: Shu-Ching Ou

Submission Date: June 26, 2018, 11:02 a.m.

Version: 1

Publication Details
Dingens AS;Haddox HK;Overbaugh J;Bloom JD,Cell Host Microbe (2017) Comprehensive Mapping of HIV-1 Escape from a Broadly Neutralizing Antibody. PMID:28579254
Additional Information

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