GENETIC RESTRICTION OF AIDS PATHOGENESIS BY AN SDF-1 CHEMOKINE GENE VARIANT

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a co receptor with CD4 for T lymphocyte cell line-tropic human immunodefici ency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identi fied in an evolutionarily conserved segment of the 3' untranslated reg ion of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (A IDS), according to a genetic association analysis of 2857 patients enr olled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV- 1 for longer periods, was twice as strong as the dominant genetic rest riction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in d elaying the onset of AIDS.