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 对感染的抗性是最常见的可变表型， 疾病结局的变化也被观察到。流行病学 研究表明，遗传因素与高血压的风险有关。 感染性病原体的死亡率。HIV-1的流行呈现出一个关键的 将现有基因技术应用于寄主研究的挑战 感染的遗传变异和感染的易感性。这 HIV-1的快速传播使HIV-1研究中的问题变得混乱 病毒的进化。 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 (CKR5delta32)存在频率为 在高加索人口中约为0.10。对1955年的考察 患者被纳入六项特征良好的艾滋病队列研究 结果显示，在612个个体中，有18个纯合子缺失 暴露于HIV-1抗体阴性的个人(2.8%)和1343人中未接触的 HIV-1感染者。CKR5缺失杂合子(+/delta32) 在HIV-1感染后存活的患者中显著升高 十多年来，在某些情况下，频率是他们的两倍 发生在艾滋病快速进展者中。清晰的生存分析 显示CKR5缺失的疾病进展较慢 杂合子。CKR5delta32缺失可能表现为隐性 限制基因对HIV-1感染的显性作用 感染患者中延缓进展为艾滋病的表型。在……里面 此外，我们还发现了CKR5基因的另外五个突变， 包括保守残基的四个错义改变和一个氨基酸 酸删除。这些改动应该会进一步增加 了解CKR5在HIV感染和疾病中的作用 进步。

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 (CKR5delta32) 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 (+/delta32) 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 CKR5delta32 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.