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

• Published in: Science (American Association for the Advancement of Science) Vol. 287; no. 5461; pp. 2274 - 2277
• Main Authors: Faure, Sophie, Meyer, Laurence, Costagliola, Dominique, Vaneensberghe, Céline, Genin, Emmanuelle, Autran, Brigitte, ALT, French, Groups, IMMUNOCO Study, Delfraissy, Jean-François, Group, SEROCO Study, McDermott, David H., Murphy, Philip M., Debré, Patrice, Théodorou, Ioannis, Combadière, Christophe
• Format: Journal Article
• Language: English
• Published: 24.03.2000
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.287.5461.2274

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 CX 3 CR1, an HIV coreceptor and leukocyte chemotactic/adhesion receptor for the chemokine fractalkine. HIV-infected patients homozygous for CX 3 CR1-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 CX 3 CR1 analysis showed that fractalkine binding is reduced among patients homozygous for this particular haplotype. Thus, CX 3 CR1-I249 M280 is a recessive genetic risk factor in HIV/AIDS.