Partial rescue of V1V2 mutant infectivity by HIV-1 cell-cell transmission supports the domain¿s exceptional capacity for sequence variation

Peter Rusert,Oliver F Brandenberg,Jürg Böni,Huldrych F Günthard,Roland R Regoes,Carsten Magnus,Alexandra Trkola,Jacqueline Weber

doi:10.1186/preaccept-1148975491133162

Peter Rusert, Oliver F Brandenberg

Open Access

https://doi.org/10.1186/preaccept-1148975491133162

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Abstract

Partial rescue of V1V2 mutant infectivity by HIV-1 cell-cell transmission supports the domain¿s exceptional capacity for sequence variation

Highlights

Variable loops 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 perform two key functions: ensuring envelope trimer entry competence and shielding against neutralizing antibodies
To establish and validate our assay setups we analyzed a panel of four JR-FL env variants for their cell-cell transmission and free virus entry capacity
Besides JR-FL wildtype we probed the V2 point mutant JR-FL I165P and V2 point mutations L175P [11] and D180N [61], which were previously described to interfere with env structural integrity and neutralization sensitivity

Summary

Introduction

Variable loops 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 perform two key functions: ensuring envelope trimer entry competence and shielding against neutralizing antibodies. Besides its role for trimer integrity, the V1V2 domain prevents premature adoption of the CD4-bound trimer conformation [16,17,18,26,27]. This is of importance for preserving a metastable trimer structure that upon receptor binding and structural rearrangements provides the energy required to complete the entry process [1,28,29]. Mutations leading to V1V2-induced transitions from a closed to an open trimer configuration result in reductions of virus entry capacity and trimer stability [3,4,5,6,7,8,9,10,11,12,13,19,20,21,22,23,24,25]

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