Related Experiment Video
Updated: Aug 16, 2026
Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3
Published on: December 27, 2010
Role of CCR5, CCR2 and SDF-1 gene polymorphisms in a population of HIV-1 infected individuals
R Mazzucchelli1, S Corvasce, M Violin
1Institute of Infectious and Tropical Diseases, University of Milan, Italy.
Abstract:
The finding that in addition to CD4 molecule HIV-1 uses, CCR5 or CXCR4 receptors to enter target cells prompted the research to identify polymorphisms in coreceptor genes affecting disease progression. In this study we analyzed the prevalence of CCR5-delta32, CCR2-641 and SDF1-3'A alleles in a highly selected group of 42 Long-Term Nonprogressors (LTNPs) compared to 112 subjects with a typical course of HIV-1 infection (TPs) and 117 healthy controls (HCs). In addition, we correlated CCR5, CCR2 and SDF-1 genotypes with molecular indexes of HIV-1 replication, cell-free RNA and both unspliced (US) and multiply spliced (MS) intracellular transcripts, to investigate the role of the mutant alleles in determining a long-term nonprogressive course of HIV-1 disease. Our results indicate a significantly higher prevalence of CCR5-delta32 allele in LTNPs compared to TPs (p=0.0434), while the proportions of CCR2-64I and SDF1-3'A alleles were comparable between the two groups. However, SDF-1 wild type LTNP subjects showed significantly lower levels of HIV-1 genomic RNA, US and MS transcripts than SDF1-3'A heterozygous ones (p=0.0021, 0.016, 0.0031, respectively), whereas both CCR5 and CCR2 wild type individuals had similar rates of viral replication compared to CCR5-delta32 and CCR2-64I heterozygous ones. CCR5, CCR2 and SDF-1 combined genotypes were also studied and this analysis did not identify a specific protective cluster of alleles in LTNPs. Taken together, our results indicate that genetic background involving CCR5, CCR2 and SDF-1 alleles may play a limited role in the natural history of HIV-1 infection.
Insights
Genetic variations in CCR5 coreceptor genes, like CCR5-delta32, may influence HIV-1 progression. However, combined gene analysis suggests a limited role for these genetic factors in long-term nonprogression of HIV-1.
Area of Science:
- Immunology
- Genetics
- Virology
Background:
- HIV-1 entry into target cells relies on CD4 and coreceptors CCR5 or CXCR4.
- Genetic polymorphisms in these coreceptor genes may impact HIV-1 disease progression.
- Understanding these genetic factors can inform strategies for managing HIV-1 infection.
Purpose of the Study:
- To investigate the prevalence of CCR5-delta32, CCR2-64I, and SDF1-3'A alleles in Long-Term Nonprogressors (LTNPs).
- To correlate coreceptor gene genotypes with molecular markers of HIV-1 replication.
- To determine the role of these genetic variations in achieving a long-term nonprogressive course of HIV-1 disease.
Main Methods:
- Genotyping analysis of CCR5-delta32, CCR2-64I, and SDF1-3'A alleles.
- Comparison of allele frequencies between LTNPs, typical progressors (TPs), and healthy controls (HCs).
- Quantification of HIV-1 replication markers: cell-free RNA, unspliced (US), and multiply spliced (MS) intracellular transcripts.
Main Results:
- The CCR5-delta32 allele was more prevalent in LTNPs than in TPs.
- No significant difference in CCR2-64I and SDF1-3'A allele proportions between LTNPs and TPs.
- SDF-1 wild-type LTNPs exhibited lower HIV-1 RNA and transcript levels compared to SDF1-3'A heterozygotes.
- Combined genotype analysis did not reveal a specific protective allele cluster in LTNPs.
Conclusions:
- The CCR5-delta32 allele may offer some protection against rapid HIV-1 disease progression.
- While individual alleles show some associations, combined genetic factors appear to play a limited role in long-term nonprogression.
- Further research is needed to fully elucidate the complex interplay of host genetics and HIV-1 pathogenesis.
