Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1

Science. 2000 Mar 24;287(5461):2274-7. doi: 10.1126/science.287.5461.2274.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Acquired Immunodeficiency Syndrome / genetics
  • Acquired Immunodeficiency Syndrome / physiopathology*
  • Acquired Immunodeficiency Syndrome / virology
  • CX3C Chemokine Receptor 1
  • Case-Control Studies
  • Chemokine CX3CL1
  • Chemokines, CX3C*
  • Chemokines, CXC / metabolism
  • Chromosomes, Human, Pair 3
  • Cohort Studies
  • Disease Progression
  • Genetic Variation
  • Genotype
  • HIV / physiology
  • HIV Infections / genetics
  • HIV Infections / physiopathology*
  • HIV Infections / virology
  • Haplotypes
  • Homozygote
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Linkage Disequilibrium
  • Membrane Proteins / metabolism
  • Mutation
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Polymorphism, Single-Stranded Conformational
  • Receptors, Cytokine / genetics*
  • Receptors, Cytokine / physiology*
  • Receptors, HIV / genetics*
  • Receptors, HIV / physiology*
  • Survival Analysis
  • White People / genetics

Substances

  • CX3C Chemokine Receptor 1
  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Chemokines, CXC
  • Membrane Proteins
  • Receptors, Cytokine
  • Receptors, HIV