Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1.
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.
Faure
S
S
Laboratoire d'Immunologie Cellulaire et Tissulaire, Centre National de la Recherche Scientifique UMR 7627, Hôpital Pitié-Salpétrière, Paris, France.
Meyer
L
L
Costagliola
D
D
Vaneensberghe
C
C
Genin
E
E
Autran
B
B
Delfraissy
J F
JF
McDermott
D H
DH
Murphy
P M
PM
Debré
P
P
Théodorou
I
I
Combadière
C
C
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
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