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Updated: Jun 30, 2026
07:06
Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
Evolution of CCR5 use before and during coreceptor switching
Mia Coetzer1, Rebecca Nedellec, Janelle Salkowitz
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Journal of Virology
|September 26, 2008
Summary
Human immunodeficiency virus type 1 (HIV-1) envelope gene evolution can lead to coreceptor switching. A decline in CCR5-using virus fitness may drive the emergence of dual-tropic R5X4 variants.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) envelope gene (env) rapidly diverges during chronic infection.
- Env evolution often leads to coreceptor switching from CCR5 to CCR5 and CXCR4, but the drivers are unclear.
Purpose of the Study:
- To investigate the functional properties of sequential env clones during HIV-1 coreceptor switching.
- To identify viral population characteristics that may drive the emergence of dual-tropic variants.
Main Methods:
- Analysis of sequential env clones from an HIV-1 infected patient.
- Evaluation of viral entry properties using CCR5 and CXCR4 coreceptors.
- Assessment of viral susceptibility to CCR5 inhibitors.
- Sequence divergence analysis of env genes, focusing on V3 and V4/V5 regions.
Main Results:
- An abrupt decline in CCR5 entry efficiency was observed at 5.67 years post-infection.
- Viruses showed increased susceptibility to CCR5 inhibitors and reduced infection of low-CCR5 cells.
- Rapid env sequence divergence (5.4%) occurred between 4.10 and 5.76 years, with positive selection in V3 and V4/V5 regions.
Conclusions:
- A decline in the fitness of CCR5-tropic (R5) HIV-1 populations may facilitate the emergence of CCR5/CXCR4-tropic (R5X4) variants.
- Viral evolution, rather than solely host factors, likely drives coreceptor switching.
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