DOI: 10.1101/472746Nov 19, 2018Paper

Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide

BioRxiv : the Preprint Server for Biology
Adam S DingensJesse D Bloom

Abstract

Resistance to enfuvirtide, the only clinically approved HIV-1 entry inhibitor, has primarily been mapped to the binding site in the N-terminal heptad repeat (NHR) of the Env transmembrane domain and a limited number of allosteric sites. To better delineate the genotypic determinants of resistance, we used deep mutational scanning to quantify how all mutations to HIV-1 Env affect enfuvirtide sensitivity. We identified numerous additional resistance mutations in the NHR and other regions of Env, including the co-receptor binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and can inform clinical monitoring of patients.

Related Concepts

Genes, env
Membrane Fusion
Terminal Repeat Sequences
Site
Inhibitors
Human immunodeficiency virus type 1 antibody
Scanning
Enfuvirtide
Gene Mutation
Monitoring - Action

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