Continuous viral escape and selection by autologous neutralizing antibodies in drug-naïve human immunodeficiency virus controllers

Madhumita Mahalanabis, Pushpa Jayaraman, Toshiyuki Miura, Florencia Pereyra, E. Michael Chester, Barbra Richardson, Bruce Walker, Nancy L. Haigwood

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

We assessed differences in the character and specificity of autologous neutralizing antibodies (ANAbs) against individual viral variants of the quasispecies in a cohort of drug-naïve subjects with long-term controlled human immunodeficiency virus type 1 (HIV-1) infection and moderate levels of broad heterologous neutralizing antibodies (HNAb). Functional plasma virus showed continuous env evolution despite a short time frame and low levels of viral replication. Neutralization-sensitive variants dominated in subjects with intermittent viral blips, while neutralization-resistant variants predominated in elite controllers. By sequence analysis of this panel of autologous variants with various sensitivities to neutralization, we identified more than 30 residues in envelope proteins (Env) associated with resistance or sensitivity to ANAbs. The appearance of new sensitive variants is consistent with a model of continuous selection and turnover. Strong ANAb responses directed against autologous Env variants are present in long-term chronically infected individuals, suggesting a role for these responses in contributing to the durable control of HIV replication.

Original languageEnglish (US)
Pages (from-to)662-672
Number of pages11
JournalJournal of virology
Volume83
Issue number2
DOIs
StatePublished - Jan 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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