HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms.

Suprit Deshpande,Rajesh Kumar,Aylur K Srikrishnan,Jayanta Bhattacharya,Suniti Solomon,Lynn Morris,Tandile Hermanus,Shilpa Patil,Kailapuri G Murugavel

doi:10.1186/s12977-016-0297-2

Abstract

The glycan supersite centered on N332 in the V3 base of the HIV-1 envelope (Env) is a target for broadly neutralizing antibodies (bnAbs) such as PGT121 and PGT128. In this study, we examined the basis of resistance of HIV-1 clade C Envs obtained from broadly cross neutralizing (BCN) plasma of an Indian donor with N332 specificity. Pseudotyped viruses expressing autologous envs were found to be resistant to autologous BCN plasma as well as to PGT121 and PGT128 mAbs despite the majority of Envs containing an intact N332 residue. While resistance of one of the Envs to neutralization by autologous plasma antibodies with shorter V1 loop length was found to be correlated with a N332S mutation, resistance to neutralization of rest of the Envs was found to be associated with longer V1 loop length and acquisition of protective N-glycans. In summary, we show evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms.

Highlights

The glycan supersite centered on N332 in the V3 base of the HIV-1 envelope (Env) is a target for broadly neutralizing antibodies such as PGT121 and PGT128
Glycan supersites in the V3 region of HIV-1 envelope form vulnerable targets that are exploited by potent and broadly neutralizing monoclonal antibodies such as PGT121 and PGT128 [25]
We examined the basis of resistance of HIV-1 clade C Envs to contemporaneous broadly cross neutralizing (BCN) plasma (INDO-SA 2007) obtained from a slow progressing Indian patient whose specificity mapped to the N332 at the V3 base

Summary

Introduction

The glycan supersite centered on N332 in the V3 base of the HIV-1 envelope (Env) is a target for broadly neutralizing antibodies (bnAbs) such as PGT121 and PGT128. By examining HIV-1 Envs obtained from BCN plasma of an Indian patient, we found that longer V1 loop length hinders the bnAbs such as PGT121 and PGT128 to access the N332 glycan epitope.

Results

Conclusion