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Updated: Jul 17, 2026

Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
Frequent intrapatient recombination between human immunodeficiency virus type 1 R5 and X4 envelopes: implications for
Mattias Mild1, Joakim Esbjörnsson, Eva Maria Fenyö
1Department of Experimental Medical Science, Lund University, BMC B13, 221 84 Lund, Sweden.
Insights
Intrapatient recombination between R5 and X4 human immunodeficiency virus type 1 (HIV-1) strains frequently creates CXCR4-using viruses. This viral evolution may contribute to disease progression and AIDS by evading immune responses and infecting CD4+ cells.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) coreceptor usage switch from CCR5 (R5) to CXCR4 (X4) correlates with disease progression to AIDS.
- Understanding the mechanisms driving this tropism switch is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the coreceptor switch in HIV-1.
- To determine the frequency and characteristics of viral recombination events contributing to CXCR4 usage.
Main Methods:
- Sequencing of 253 V1 to V3 env clones from sequential HIV-1 subtype B isolates from four patients exhibiting coreceptor switching.
- Experimental characterization of coreceptor usage for dualtropic R5X4 isolates.
- Sequence analysis to identify recombination events.
Main Results:
- Recombination between R5 and X4 viruses was identified as a frequent event (9% of clones from CXCR4-using isolates).
- The majority (73%) of identified recombinants utilized CXCR4.
- A small region of the viral envelope, including V3, was found to determine the coreceptor usage of these recombinants.
Conclusions:
- Intrapatient recombination between HIV-1 strains with distinct coreceptor usage occurs frequently.
- Chimeric viruses resulting from recombination can evade immune surveillance and infect CXCR4-expressing cells, potentially contributing to immune system impairment.
- This recombination mechanism may play a significant role in the emergence of X4 viruses during later stages of HIV-1 infection.
Abstract:
Emergence of human immunodeficiency virus type 1 (HIV-1) populations that switch or broaden coreceptor usage from CCR5 to CXCR4 is intimately coupled to CD4+ cell depletion and disease progression toward AIDS. To better understand the molecular mechanisms involved in the coreceptor switch, we determined the nucleotide sequences of 253 V1 to V3 env clones from 27 sequential HIV-1 subtype B isolates from four patients with virus populations that switch coreceptor usage. Coreceptor usage of clones from dualtropic R5X4 isolates was characterized experimentally. Sequence analysis revealed that 9% of the clones from CXCR4-using isolates had originated by recombination events between R5 and X4 viruses. The majority (73%) of the recombinants used CXCR4. Furthermore, coreceptor usage of the recombinants was determined by a small region of the envelope, including V3. This is the first report demonstrating that intrapatient recombination between viruses with distinct coreceptor usage occurs frequently. It has been proposed that X4 viruses are more easily suppressed by the immune system than R5 viruses. We hypothesize that recombination between circulating R5 viruses and X4 viruses can result in chimeric viruses with the potential to both evade the immune system and infect CXCR4-expressing cells. The broadening in cell tropism of the viral population to include CXCR4-expressing cells would gradually impair the immune system and eventually allow the X4 population to expand. In conclusion, intrapatient recombination between viruses with distinct coreceptor usage may contribute to the emergence of X4 viruses in later stages of infection.
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