Rapid Progression to AIDS in HIV + Individuals with a Structural Variant of the Chemokine Receptor CX 3 CR1

Abstract

Human immunodeficiency virus (HIV) enters cells in vitro via CD4 and a coreceptor. Which of 15 known coreceptors are important in vivo is poorly defined but may be inferred from disease-modifying mutations, as for CCR5. Here two single nucleotide polymorphisms are described in Caucasians in CX₃CR1, an HIV coreceptor and leukocyte chemotactic/adhesion receptor for the chemokine fractalkine. HIV-infected patients homozygous for CX₃CR1-I249 M280, a variant haplotype affecting two amino acids (isoleucine-249 and methionine-280), progressed to AIDS more rapidly than those with other haplotypes. Functional CX₃CR1 analysis showed that fractalkine binding is reduced among patients homozygous for this particular haplotype. Thus, CX₃CR1-I249 M280 is a recessive genetic risk factor in HIV/AIDS.