A variant of SDF-1, the ligand for CXCR4, delays progression to AIDS and death

The rate of progression to AIDS in HIV-1 infected individuals is under at least partial control by host genetic factors. Protective genotypes for variant alleles of the CCR2 and CCR5 chemokine receptors have been shown to delay progression to AIDS by two to four years in large cohort studies. Stromal derived factor, SDF-1, is the principal ligand of CXCR4, a co-receptor for T-tropic HIV-1 strains. A common polymorphism, 801G >/= A, named SDF1 3'A, was identified in the SDF1beta structural gene transcript in an evolutionarily conserved region of the 3' untranslated region. Survival and association analysis of 2654 participants enrolled in 5 cohort studies showed that in the recessive state, SDF1-3'A/3'A delayed progression to AIDS and death. An enrichment of SDF1 3'A homozygotes in patients infected for longer time intervals was also observed. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods and twice as strong as the dominant protection conferred by either CCR2 or CCR5. Protection with a CCR2 or CCR5 protective allele and the SDF1-3'A/3'A genotype is additive and significantly increases survival in patients with dual protection.

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