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 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.
Mazzucchelli
R
R
Institute of Infectious and Tropical Diseases, University of Milan, Italy.
Corvasce
S
S
Violin
M
M
Riva
C
C
Bianchi
R
R
Dehò
L
L
Velleca
R
R
Cibella
J
J
Bada
M
M
Moroni
M
M
Galli
M
M
Balotta
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000483:Alleles; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*
C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine