Investigation of the factors influencing on HIV mother-to-child transmission and disease progression

(1)影响HIV-1母婴传播的因素和疾病进展的调查：在大多数艾滋病毒母婴传播病例都存在的非洲，关于影响HIV-1母婴传播的因素的报道很少，宿主免疫因素对临床病程的影响还没有得到证实。在肯尼亚西部使用短程齐多夫定(ZDV)预防母婴传播的队列研究中，我们发现，在母亲服用ZDV的婴儿中，CCR5-2132T/T和-2554T/T与HIV-1母婴的母婴母在婴儿HIV-1克隆中未观察到ZDV耐药相关突变，在母亲治疗前后的部分HIV-1克隆中观察到部分ZDV耐药相关突变，但均为二次突变。这些结果表明，尽管短期接受ZDV治疗，HIV-1的MTCT与ZDV耐药突变的诱导无关。(2)影响HIV感染日本血友病患者临床病程的因素：我们先前报道了CCR5启动子区域的SNPs与HIV-1感染的日本血友病患者临床病程的关系。在本研究中，我们进一步分析了RANTES启动子-28G/-403A、RANTESIN1.1C、SDF-1 3‘A、IL-4启动子-589T和DC-SIGN启动子-139C/-336C等SNPs与疾病进展的关系，发现RANTES-28G与延缓艾滋病进展有关，而DCSIGN-139C与HIV-1感染的日本血友病患者加速艾滋病进展有关。

(1)Investigation of the factors influencing on mother-to-child transmission (MTCT) of HIV-1 and disease progression : There have been few reports on the factors influencing on HIV-1 MTCT in Africa, where most cases of HIV MTCT exist, and the effect of host immune factors on clinical course left unconfirmed. In the cohort study on the prevention of MTCT using short course zidovudine (ZDV) in western Kenya, we found that CCR5-2132T/T and -2554T/T were associated with increased HIV-1 MTCT and RANTES-403 A/A was associated with decreased MTCT among infants whose mother took ZDV, and that no SNP (single nucleotide polymorphism) analyzed in the study was found to be associated with mortality rate at the age of 24 months. In addition, no ZDV-resistant associated mutation was observed in infants' HIV-1 clones, and some ZDV-resistant associated mutations were observed in a part of HIV-1 clones sampled from the mothers before and after ZDV-treatment, but they were all secondary mutations. These results suggest that the cause of MTCT of HIV-1 in spite of short-term ZDV treatment was not associated with an induction of ZDV-resistant mutants.(2)Factors influencing on the clinical courses among HIV-infected Japanese hemophiliacs : We previously reported the relationship between SNPs in the CCR5 promoter region and the clinical courses in HIV-1-infected Japanese hemophiliacs. In the current study, we further analyzed the relationship between the SNPs, such as RANTES promoter-28G/-403A, RANTESIn1.1C, SDF-1 3'A, IL-4 promoter-589T and DC-SIGNpromoter-139C/-336C, and disease progression, and found that RANTES-28G was associated with delayed AIDS progression, while DCSIGN-139C was associated with accelerated AIDS progression in HIV-1-infected Japanese hemophiliacs.