Continuous Viral Escape and Selection by Autologous Neutralizing Antibodies in Drug-Naïve Human Immunodeficiency Virus Controllers
- 15 January 2009
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 83 (2), 662-672
- https://doi.org/10.1128/jvi.01328-08
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.Keywords
This publication has 33 references indexed in Scilit:
- Heavily glycosylated, highly fit SIVMne variants continue to diversify and undergo selection after transmission to a new host and they elicit early antibody dependent cellular responses but delayed neutralizing antibody responsesVirology Journal, 2008
- Viral Phenotypes and Antibody Responses in Long-Term Survivors Infected with Attenuated Human Immunodeficiency Virus Type 1 Containing Deletions in thenefand Long Terminal Repeat RegionsJournal of Virology, 2007
- Broad HIV-1 neutralization mediated by CD4-binding site antibodiesNature Medicine, 2007
- Evidence for Persistent, Occult Infection in Neonatal Macaques following Perinatal Transmission of Simian-Human Immunodeficiency Virus SF162P3Journal of Virology, 2007
- Neutralizing Antibody Responses against Autologous and Heterologous Viruses in Acute versus Chronic Human Immunodeficiency Virus (HIV) Infection: Evidence for a Constraint on the Ability of HIV To Completely Evade Neutralizing Antibody ResponsesJournal of Virology, 2006
- Multiple sequence alignment with the Clustal series of programsNucleic Acids Research, 2003
- Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic feverNature Medicine, 2003
- Antibody neutralization and escape by HIV-1Nature, 2003
- A Direct Approach to False Discovery RatesJournal of the Royal Statistical Society Series B: Statistical Methodology, 2002
- Tracking Changes in HIV-1 Envelope Quasispecies Using DNA Heteroduplex AnalysisMethods, 1997