ROLE OF CHEMOKINES AND CHEMOKINE RECEPTORS IN AIDS

在所有具有良好特征的流行病中，都有个人 对传染病病原体有不同反应的人群。虽然 对感染的抵抗力是最常见的变异表型、变异 在疾病结果中也观察到了。流行病学研究表明 表明遗传因素与死亡的风险有关 感染剂。艾滋病毒-1的流行对 应用现代遗传技术研究寄主遗传变异 用于感染和对感染的敏感性。这个问题是 在HIV-1的研究中被快速进化的 病毒。 CKR5基因作为CD4+T淋巴细胞的二级受体 人类免疫缺陷病毒的某些毒株。CKR5基因是 被定位到人类染色体3p21，以及一个32碱基对缺失等位基因 (CKR5D32)被鉴定为以大约 在高加索人口中为0.10。1955例患者的检查结果 包括在六项特征良好的艾滋病队列研究中显示 在612例暴露于HIV-1的人中，18例纯合子完全缺失 1343例HIV-1感染者中抗体阴性者(2.8%)和非感染者 个人。CKR5缺失杂合子(+/D32) 在HIV-1感染存活超过10年的患者中升高 几年来，在某些情况下，它们的出现频率是在快速 艾滋病的进步者。生存分析清楚地表明，疾病 CKR5缺失杂合子的进展较慢。CKR5D32 缺失可能是抗HIV-1感染的隐性限制基因 并在以下人群中发挥了延缓艾滋病进展的主导表型 被感染的病人。此外，我们还确认了另外五个 CKR5基因的改变，包括4个错义改变 保守残基，氨基酸缺失。这些改动应该 进一步加深对CKR5在HIV感染中的作用的理解 和疾病的进展。

In all well-characterized epidemics there are individuals in the population that respond differently to the infectious agent. Although resistance to infection is the most common variable phenotype, variation in disease outcomes has also been observed. Epidemiologic studies have shown that inherited factors are involved in the risk of mortality to infectious agents. The HIV-1 epidemic presents a critical challenge to apply current genetic techniques to the study of host genetic variation for infection and susceptibility to infection. This problem is confounded in the studies of HIV-1 by the rapid rate of evolution of the virus. The CKR5 gene serves as a secondary receptor on CD4+ T lymphocytes for certain strains of human immunodeficiency virus. The CKR5 gene was mapped to human chromosome 3p21, and a 32 base pair deletion allele (CKR5D32) was identified that is present at a frequency of approximately 0.10 in the Caucasian population. An examination of 1955 patients included among six well-characterized AIDS cohort studies revealed that 18 deletion homozygotes occur exclusively among 612 exposed HIV-1- antibody negative individuals (2.8%) and not in 1343 HIV-1-infected individuals. CKR5 deletion heterozygotes (+/D32) were significantly elevated among patients that survive HIV-1 infection for more than 10 years, in some cases twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes. The CKR5D32 deletion may act as a recessive restriction gene against HIV-1 infection and exerts a dominant phenotype of delaying progression to AIDS among infected patients. In addition, we have identified five other alterations in the CKR5 gene, including four missense alterations in conserved residues, and an amino acid deletion. These alterations should further add to the understanding of the role of CKR5 in HIV infection and disease progression.