Rapid Progression to AIDS in HIV + Individuals with a Structural Variant of the Chemokine Receptor CX 3 CR1-Reference-Cited by-同舟云学术

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

Published:2000-03-24 Issue:5461 Volume:287 Page:2274-2277
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Faure Sophie¹,Meyer Laurence²,Costagliola Dominique³,Vaneensberghe Céline¹,Genin Emmanuelle⁴,Autran Brigitte¹,ALT French,Groups IMMUNOCO Study,Delfraissy Jean-François⁵,Group SEROCO Study,McDermott David H.⁶,Murphy Philip M.⁶,Debré Patrice¹,Théodorou Ioannis¹,Combadière Christophe¹⁶⁷

Affiliation:

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, Facultéde 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.

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 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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