PT  - JOURNAL ARTICLE
AU  - Adam S. Dingens
AU  - Dana Arenz
AU  - Julie Overbaugh
AU  - Jesse D. Bloom
TI  - Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide
AID  - 10.1101/472746
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 472746
4099  - http://biorxiv.org/content/early/2018/11/19/472746.short
4100  - http://biorxiv.org/content/early/2018/11/19/472746.full
AB  - 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.