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

The finding that in addition to CD4 molecule HIV-1 uses, CCR5 or CXCR4 rece ptors to enter target cells prompted the research to identify polymorphisms in coreceptor genes affecting disease progression. In this study we analyz ed the prevalence of CCR5-Delta 32, CCR2-641 and SDF1-3'A alleles in a high ly selected group of 42 Long-Term Nonprogressors (LTNPs) compared to 112 su bjects with a typical course of HIV-1 infection (TPs) and 117 healthy contr ols (HCs). In addition, we correlated CCR5, CCR2 and SDF-1 genotypes with m olecular indexes of HIV-1 replication, cell-free RNA and both unspliced (US ) and multiply spliced (MS) intracellular transcripts, to investigate the r ole of the mutant alleles in determining a long-term nonprogressive course of HIV-1 disease. Our results indicate a significantly higher prevalence of CCR5-Delta 32 allele in LTNPs compared to TPs (p = 0.0434), while the prop ortions of CCR2-641 and SDF1-3'A alleles were comparable between the two gr oups. However, SDF-1 wild type LTNP subjects showed significantly lower lev els 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 CC R5-Delta 32 and CCR2-641 heterozygous ones. CCR5, CCR2 and SDF-1 combined g enotypes were also studied and this analysis did not identify a specific pr otective cluster of alleles in LTNPs. Taken together, our results indicate that genetic background involving CCR5, CCR2 and SDF-1 alleles may play a l imited role in the natural history of HIV-1 infection.