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

Retrovirology. 2016 Aug 30;13(1):60. 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.

Keywords: Envelope; HIV-1; Neutralizing antibody; Plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • HIV Antibodies / chemistry
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Humans
  • Mutation
  • Neutralization Tests
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • Polysaccharides / immunology*
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Antibodies, Neutralizing
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Polysaccharides
  • env Gene Products, Human Immunodeficiency Virus