Role of CCR5, CCR2 and SDF-1 gene polymorphisms in a population of HIV-1 infected individuals

R. Mazzucchelli, S. Corvasce, M. Violin, C. Riva, R. Bianchi, L. Dehò, R. Velleca, J. Cibella, M. Bada, M. Moroni, M. Galli, C. Ballotta

Research output: Contribution to journalArticlepeer-review

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-Δ32, 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-Δ32 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-Δ32 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.

Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalJournal of Biological Regulators and Homeostatic Agents
Volume15
Issue number3
Publication statusPublished - 2001

Keywords

  • CCR2-64I
  • CCR5-Δ32
  • HIV-1 genomic RNA
  • LTNPs
  • SDF1-3′A
  • US and MS intracellular specific transcripts

ASJC Scopus subject areas

  • Immunology
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Physiology (medical)
  • Medicine (miscellaneous)
  • Physiology
  • Agricultural and Biological Sciences(all)

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