Rapid progression to AIDS in HIV+ individuals with a structural variant ofthe chemokine receptor CX(3)CR1

Human immunodeficiency virus (HIV) enters cells in vitro via CD4 and a core ceptor. Which of 15 known coreceptors are important in vivo is poorly defin ed but may be inferred from disease-modifying mutations, as for CCR5, Here two single nucleotide polymorphisms are described in Caucasians in CX(3)CR1 , an HIV coreceptor and leukocyte chemotactic/adhesion receptor for the che mokine fractalkine. HIV-infected patients homozygous for CX(3)CR1-1249 M280 , a variant haplotype affecting two amino acids (isoleucine-249 and methion ine-280), progressed to AIDS more rapidly than those with other haplotypes. Functional CX(3)CR1 analysis showed that fractalkine binding is reduced am ong patients homozygous for this particular haplotype. Thus, CX(3)CR1-1249 M280 is a recessive genetic risk factor in HIV/AIDS.