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

Publication date: Available online 1 June 2017
Source:Cell Host & Microbe
Author(s): Adam S. Dingens, Hugh K. Haddox, Julie Overbaugh, Jesse D. Bloom
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.

Graphical abstract

Teaser

Dingens et al. developed a massively parallel approach to quantify how all mutations to HIV Env affect antibody neutralization in the context of replication-competent virus. They applied this approach to the antibody PGT151, validated the results with neutralization assays, and explored the biochemical basis of HIV escape from this antibody.


http://ift.tt/2rzVsWE