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 journalArticle

    85 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 1 2009

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    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

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