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

By Adam S. Dingens, Dana Arenz, Julie Overbaugh, Jesse Bloom

Posted 19 Nov 2018
bioRxiv DOI: 10.1101/472746 (published DOI: 10.3390/v11050439)

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.

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