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Science 24 March 2000:
Vol. 287. no. 5461, pp. 2274 - 2277
DOI: 10.1126/science.287.5461.2274
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Reports

Rapid Progression to AIDS in HIV+ Individuals with a Structural Variant of the Chemokine Receptor CX3CR1

Sophie Faure, 1 Laurence Meyer, 2 Dominique Costagliola, 3 Céline Vaneensberghe, 1 Emmanuelle Genin, 4 Brigitte Autran, 1 French ALT, and IMMUNOCO Study Groups, Jean-François Delfraissy, 5 SEROCO Study Group, David H. McDermott, 6 Philip M. Murphy, 6 Patrice Debré, 1 Ioannis Théodorou, 1* Christophe Combadière 167

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.

1 Laboratoire d'Immunologie Cellulaire et Tissulaire, Centre National de la Recherche Scientifique UMR 7627, Hôpital Pitié-Salpétrière, Paris, France.
2 Institut National de la Santé et de la Recherche Médicale U292, Département d'Epidémiologie, Hôpital de Bicêtre, Faculté de Médecine, Kremlin-Bicêtre, France.
3 Institut National de la Santé et de la Recherche Médicale SC4, Faculté de Médecine Saint-Antoine, Paris, France.
4 Institut National de la Santé et de la Recherche Médicale U155, Hôpital de Bicêtre, Kremlin-Bicêtre, France.
5 Service de Médecine Interne, Hôpital de Bicêtre, Kremlin-Bicêtre, France.
6 Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
7 Institut National de la Santé et de la Recherche Médicale U479, CHU Bichat, Paris, France.
*   To whom correspondence should be addressed: E-mail: ioannis.theodorou{at}psl.ap-hop-paris.fr

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