Mechanistic Analysis of the Broad Antiretroviral Resistance Conferred by HIV-1 Envelope Glycoprotein Mutations
Yuta Hikichi, Rachel Van Duyne, Phuong Pham, Jennifer L. Groebner, Ann Wiegand, John W. Mellors, Mary F. Kearney, Eric O. Freed
Abstract
We demonstrate that Env mutations can reduce sensitivity to major classes of ARVs in multiple viral isolates and define the effect of the Env mutations on Env subunit interactions. We observed that many Env mutations accumulated in individuals failing integrase inhibitor therapy despite a low frequency of resistance mutations in integrase. Our findings suggest that broad-based Env-mediated drug resistance may impact therapeutic strategies and provide clues toward understanding how ARV-treated individuals fail therapy without acquiring mutations in drug target genes.
Topics & Concepts
VirologyGlycoproteinDrug resistanceHuman immunodeficiency virus (HIV)MutationAntiretroviral therapyAntiretroviral drugBiologyGeneEnvelope (radar)MedicineImmunologyGeneticsViral loadComputer scienceRadarTelecommunicationsHIV Research and TreatmentHIV/AIDS drug development and treatmentHIV/AIDS Research and Interventions