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

S Faure, L Meyer, D Costagliola, C Vaneensberghe… - Science, 2000 - science.org
S Faure, L Meyer, D Costagliola, C Vaneensberghe, E Genin, B Autran, F ALT, IS Groups…
Science, 2000science.org
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 …
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.
AAAS