Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1
Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1
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DOI：
10.1126/science.287.5461.2274
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发表时间：
2000-03-24
期刊：
影响因子：
56.9
通讯作者：
Combadière, C
中科院分区：
文献类型：
--
作者：
Faure, S;Meyer, L;Combadière, C
人类免疫缺陷病毒（HIV）在体外通过CD 4和辅助受体进入细胞。在15种已知的辅助受体中，哪一种在体内是重要的还不清楚，但可以从疾病修饰突变中推断出来，如CCR 5，这里描述了高加索人CX（3）CR 1的两种单核苷酸多态性，CX（3）CR 1是HIV辅助受体和趋化因子fractalkine的白细胞趋化/粘附受体。CX（3）CR 1 -1249 M280纯合子的HIV感染者比其他单倍型患者更快地发展为AIDS。CX（3）CR 1 -1249 M280是一种影响两个氨基酸（异亮氨酸-249和甲硫氨酸-280）的变异单倍型。功能性CX（3）CR 1分析表明，在这种特定单倍型纯合子患者中，fractalkine结合减少。因此，CX（3）CR 1 -1249 M280是HIV/AIDS的隐性遗传危险因子。
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)CR1-1249 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)CR1-1249 M280 is a recessive genetic risk factor in HIV/AIDS.