Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1

  • Science. 2000 Mar 24;287(5461):2274-7. doi: 10.1126/science.287.5461.2274.
S Faure  1 ,  L Meyer ,  D Costagliola ,  C Vaneensberghe ,  E Genin ,  B Autran ,  J F Delfraissy ,  D H McDermott ,  P M Murphy ,  P Debré ,  I Théodorou ,  C Combadière
Affiliations
  • 1. Laboratoire d'Immunologie Cellulaire et Tissulaire, Centre National de la Recherche Scientifique UMR 7627, Hôpital Pitié-Salpétrière, Paris, France.
PMID: 10731151 DOI: 10.1126/science.287.5461.2274
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.