Host genetic polymorphisms that can affect HIV diseases.

1. CCR5 是人类免疫缺陷病毒 1 型 (HIV-1) R5 株进入细胞的重要辅助受体。 CCR5-893(-) 是一种单核苷酸缺失突变，仅在亚洲人中观察到。我们发现CCR5-893(-)突变影响CCR5的细胞内转运，并提出该突变也影响HIV-1传播和疾病进展的可能性。2． CCR2 (CCR2-64I) 64 位缬氨酸替换为异亮氨酸与 HIV-1 感染者延迟发展为 AIDS 相关。我们的结果表明，CCR2 (CCR2A) 的 A 亚型与细胞质中的 CCR5 结合并下调其表面表达。我们认为，CCR2A-64I 下调 CCR5 表达的能力增强可能是具有该等位基因的患者 HIV-1 疾病进展延迟的一个可能原因。3。白细胞介素(IL)-4-589T等位基因在IL-4基因开放阅读框上游第89位具有单核苷酸多态性。在法国 SEROCO 队列中，携带 IL-4-589T 的患者血清病毒载量低于不携带该等位基因的患者 (P=0.02)。 Kaplan-Meier 分析生存曲线显示 IL-4-589T 携带者向临床 AIDS 的进展较慢（P=0.04）。这些结果表明IL-4-589T 通过减少病毒载量来防止HIV-1 疾病进展。4．通过 PCR-RFLP 对总共 246 份泰国女性样本进行了 IL4 和 RANTES 启动子多态性基因分型。我们的结果表明 IL4-589T 和 RANTES-28G 对泰国人的 HIV 疾病进展具有显着的保护作用。相比之下，没有 RANTES-28G 的 RANTES In1.1C 对 HIV 疾病进展有加速作用。

1. CCR5 is an essential coreceptor for the cellular entry of R5 strains of human immunodeficiency virus type 1 (HIV-1). CCR5-893(-) is a single-nucleotide deletion mutation which is observed exclusively in Asians. We found that the CCR5-893(-) mutation affects intracellular transport of CCR5 and raise the possibility that this mutation also affects HIV-1 transmission and disease progression.2. A valine to isoleucine substitution at position 64 of CCR2 (CCR2-64I) is associated with a delay in progression to AIDS in HIV-1-infected individuals. Our results suggest that an A isoform of CCR2 (CCR2A) binds to CCR5 in the cytoplasm and down-modulates its surface expression. We propose that the increased ability of CCR2A-64I to down-modulate CCR5 expression might be a possible cause of a delay in HIV-1 disease progression in patients with this allele.3. The interleukin (IL)-4-589T allele bears a single nucleotide polymorphism at position・89 upstream from the open-reading frame of the IL-4 gene. Serum virus load was lower in patients with IL-4-589T than in those without this allele (P=0.02) in the French SEROCO cohort. Kaplan-Meier analysis survival curves showed a slower progression to clinical AIDS in carriers of IL-4-589T (P=0.04). These results suggest that IL-4-589T protects against HIV-1 disease progression by reducing virus load.4. A total of 246 Thai female samples were genotyped for IL4 and RANTES promoter polymorphisms by PCR-RFLP. Our results implicate the significant protective effect of IL4-589T and RANTES-28G on HIV disease progression in Thais. In contrast, RANTES In1.1C without RANTES-28G had an accelerating effect on HIV disease progression.