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Updated: Aug 19, 2026

Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
CXCR4 as a functional coreceptor for human immunodeficiency virus type 1 infection of primary macrophages
G Simmons1, J D Reeves, A McKnight
1Section of Virology, Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB, United Kingdom.
Abstract:
The coreceptors used by primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates for infection of primary macrophages were investigated. SI strains using only CXCR4 replicated equally well in macrophages with or without CCR5 and were inhibited by several different ligands for CXCR4 including SDF-1 and bicyclam derivative AMD3100. SI strains that used a broad range of coreceptors including CCR3, CCR5, CCR8, CXCR4, and BONZO infected CCR5-deficient macrophages about 10-fold less efficiently than CCR5(+) macrophages. Moreover, AMD3100 blocked infection of CCR5-negative macrophages by these strains. Our results therefore demonstrate that CXCR4, as well as CCR5, is used for infection of primary macrophages but provide no evidence for the use of alternative coreceptors.
Insights
Primary human immunodeficiency virus type 1 (HIV-1) strains utilize CXCR4 and CCR5 coreceptors for macrophage infection. While CXCR4 is sufficient, some strains also use CCR5, with AMD3100 inhibiting infection.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) entry into host cells requires coreceptors.
- Syncytium-inducing (SI) HIV-1 strains infect various cell types, including macrophages.
- The specific coreceptors utilized by SI HIV-1 for macrophage infection are not fully elucidated.
Purpose of the Study:
- To investigate the coreceptors used by primary syncytium-inducing (SI) HIV-1 isolates for infection of primary macrophages.
- To determine the role of CXCR4 and CCR5 in SI HIV-1 macrophage tropism.
- To assess the impact of coreceptor usage on viral replication efficiency.
Main Methods:
- Infection of primary macrophages with SI HIV-1 isolates.
- Assessment of viral replication in macrophages with varying CCR5 expression levels.
- Inhibition studies using CXCR4 ligands, including AMD3100.
Main Results:
- SI HIV-1 strains utilizing only CXCR4 replicated efficiently in macrophages regardless of CCR5 expression.
- These CXCR4-dependent strains were inhibited by CXCR4 ligands like AMD3100.
- SI strains using multiple coreceptors (including CCR5) showed reduced infection efficiency in CCR5-deficient macrophages and were inhibited by AMD3100.
Conclusions:
- CXCR4 is a crucial coreceptor for SI HIV-1 infection of primary macrophages.
- CCR5 can also be utilized by certain SI HIV-1 strains, but it is not essential when CXCR4 is available.
- These findings provide no evidence for the use of alternative coreceptors beyond CXCR4 and CCR5 in this context.
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