title: Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1.
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.
authors.affiliation: Laboratoire d'Immunologie Cellulaire et Tissulaire, Centre National de la Recherche Scientifique UMR 7627, Hôpital Pitié-Salpétrière, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Faure
authors.forename: L
authors.initials: L
authors.lastname: Meyer
authors.forename: D
authors.initials: D
authors.lastname: Costagliola
authors.forename: C
authors.initials: C
authors.lastname: Vaneensberghe
authors.forename: E
authors.initials: E
authors.lastname: Genin
authors.forename: B
authors.initials: B
authors.lastname: Autran
authors.forename: J F
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: D H
authors.initials: DH
authors.lastname: McDermott
authors.forename: P M
authors.initials: PM
authors.lastname: Murphy
authors.forename: P
authors.initials: P
authors.lastname: Debré
authors.forename: I
authors.initials: I
authors.lastname: Théodorou
authors.forename: C
authors.initials: C
authors.lastname: Combadière
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000503:physiopathology* / Q000821:virology; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000378:metabolism; D002893:Chromosomes, Human, Pair 3; D015331:Cohort Studies; D018450:Disease Progression; D014644:Genetic Variation; D005838:Genotype; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000235:genetics / Q000503:physiopathology* / Q000821:virology; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D018121:Receptors, Cytokine / Q000235:genetics* / Q000502:physiology*; D015728:Receptors, HIV / Q000235:genetics* / Q000502:physiology*; D016019:Survival Analysis; D044465:White People / Q000235:genetics
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV