Host genetic polymorphisms that can affect HIV diseases.

1. CCR5是R5 strains of human immunodeficiency的一部分virus type 1 . CCR5-893(-) is a single-nucleotide deletion mutation which is observedexclusively in Asians.我们发现CCR5-893(-) mutation affects intracellular transport ofCCR5 and raise the possibility that mutation also affects HIV-1 transmission and diseaseprogression.2. A valine to isoleucine substitution at position 64 of CCR2 （CCR2- 64i）是相关的with a delay in progression to AIDS in HIV-1-infected individuals. Our results suggest that aisoform of CCR2 (CCR2A) binds to CCR5 in the cytoplasm and down-modulates its surface表达式. We提供给CCR2A-64I to down-modulate CCR5的附加能力可能性cause of a delay in HIV-1 disease progression in patients with this allele.3interleukin (IL)-4-589T allele bears a single nucleotide polymorphism at position 89 upstream fromopen-reading frame of the IL-4 gene. Serum virus load was lower in patients with IL-4- 589t thanin those without this allele (P=0.02) in the French SEROCO cohort. Kaplan-Meier分析survivalcurves showed a slow progression to clinical AIDS in carriers of IL-4-589T (P=0.04). These resultssuggest that IL-4-589T protects against HIV-1疾病progression by reducing virus load.4. A totalof 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 diseaseprogression in Thais. in contrast，RANTES In1.1C without RANTES- 28g had an accelerating effect on HIV disease progression

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.