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bioRxiv · 10.1101/472746

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

Dingens, A. S.·Arenz, D.·Overbaugh, J.·Bloom, J. D.
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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.

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Dingens, A. S., Arenz, D., Overbaugh, J., Bloom, J. D.. 2018-11-19. Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide. https://doi.org/10.1101/472746

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