Common evolutionary features of the envelope glycoprotein of HIV-1 in patients belonging to a transmission chain

Maxime Beretta,Martine Braibant,Francis Barin,Mélanie Bouvin-Pley,Asma Essat,Alain Moreau,Laurence Meyer,Julie Migraine,Cécile Goujard,Marie-Laure Chaix,Aurélie Drouin

doi:10.1038/s41598-020-73975-4

Abstract

The diversity of the HIV-1 envelope glycoproteins (Env) is largely a consequence of the pressure exerted by the adaptive immune response to infection. While it was generally assumed that the neutralizing antibody (NAb) response depended mainly on the infected individual, the concept that virus-related factors could be important in inducing this response has recently emerged. Here, we analyzed the influence of the infecting viral strain in shaping NAb responses in four HIV-1 infected subjects belonging to a transmission chain. We also explored the impact of NAb responses on the functional evolution of the viral quasispecies. The four patients developed a strong autologous neutralizing antibody response that drove viral escape and coincided with a parallel evolution of their infecting quasispecies towards increasing infectious properties, increasing susceptibility to T20 and increasing resistance to both CD4 analogs and V3 loop-directed NAbs. This evolution was associated with identical Env sequence changes at several positions in the V3 loop, the fusion peptide and the HR2 domain of gp41. The common evolutionary pattern of Env in different hosts suggests that the capacity of a given Env to adapt to changing environments may be restricted by functional constraints that limit its evolutionary landscape.

Highlights

The diversity of the HIV-1 envelope glycoproteins (Env) is largely a consequence of the pressure exerted by the adaptive immune response to infection
In a small subset of cases, this will lead after years of infection to the development of broadly neutralizing antibodies able to block infection by heterologous viruses belonging to various subtypes in vitro[21,22,23]
The purpose of our study was to study if this virus-dictated heritability of neutralizing antibody (NAb) responses could be observed in four HIV-1 infected subjects belonging to a transmission chain, and to what extent the NAb response impacts the functional Env properties of the evolving viral quasispecies

Summary

Introduction

The diversity of the HIV-1 envelope glycoproteins (Env) is largely a consequence of the pressure exerted by the adaptive immune response to infection. The analysis of the antibody responses of HIV-1 infected individuals identified as transmission pairs within the Swiss cohort suggested that the NAb response could be imprinted by the nature of the infecting strain[45] This new concept is crucial for the design of effective immunogens able to induce similar bNAbs responses across vaccinees. In this context, the purpose of our study was to study if this virus-dictated heritability of NAb responses could be observed in four HIV-1 infected subjects belonging to a transmission chain, and to what extent the NAb response impacts the functional Env properties of the evolving viral quasispecies. A better knowledge of mutable sites versus those vulnerable to mutations will help with the rational design of Env immunogens for effective vaccines

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Conclusion