STUDY ON MOLECULAR EPIDEMIOLOGY OF HIV AND HOST FACTOR INFLUENCING DISEASE PROGRESSION IN ASIA

(A)亚洲艾滋病毒分子流行病学研究(武部博士)1)越南北部艾滋病毒暴发的分子流行病学：我们调查了越南北部注射吸毒者最近艾滋病毒暴发的分子性质。我们发现，分布在越南北部静脉吸毒人群中的CRF01AE毒株与广西凭祥的中国毒株有着密切的亲缘关系，在V3环下游的12个氨基酸上有一个独特的Valine替换。数据表明，越南北部注射吸毒者中的艾滋病毒暴发是由于最近引入了高度同源的CRF01_AE变种(EV变种)，该变种与邻近中国南方流行的艾滋病毒-1的起源相同。2)艾滋病毒-1独特重组形式在缅甸的高流行率：我们发现在缅甸流行的艾滋病毒-1毒株中有10%-30%是不同形式的艾滋病毒-1亚型重组体，包括三种艾滋病毒-1毒株的不同组合，包括艾滋病毒-1 B‘亚型(…亚型的泰国变种更多的B)和C和CRF01_AE型，在缅甸流行。3)云南省HIV-1亚型间广泛重组的地理热点中国：云南省被认为是中国暴发流行的中心。我们在云南省西部确定了一个独特的地理位置，那里大约2/3的流行毒株是HIV-1独特的重组形式(URF)。我们还发现了由先前在中国中建立的两种循环重组形式(CRF07_BC和CRF08_BC)组成的新的HIV-1重组体。结果表明，不同HIV-1毒株的混合可以迅速产生各种形式的重组体。(B)泰国人群中影响HIV-1易感性和疾病进展的宿主遗传因素研究(Shioda博士)：对泰国不和谐夫妇进行的横断面研究显示，CCR5 927T突变是泰国人群中与抵抗HIV-1感染有关的重要遗传易感性。这项基于泰国北部队列的研究证实，在女性人群和接受HAART治疗的患者中，1L4-589T纯合性和疾病进展缓慢之间存在关联。(C)亚洲未来疫苗策略的免疫学研究(Takiguchi博士和Yasutomi博士)：Takiguchi博士的团队表征了HIV-1 B亚型和CRF01_AE感染的泰国和日本患者对HIV-1交叉分支和分支特异性表位的细胞毒性T细胞识别。Yasutomi博士和他的同事开发了基于戊型肝炎病毒病毒样颗粒(VLP)的新型口服疫苗载体，这种载体允许整合DNA疫苗结构并诱导体液和细胞毒性T细胞反应。较少

(A)Study on Molecular epidemiology of HIV in Asia (Dr. Takebe)1)Molecular epidemiology of HIV outbreaks in Northern Vietnam:We investigated the molecular nature of recent HIV outbreaks among injecting drug users (IDUs) in Northern Vietnam. We found that CRF01_AE strains distributed among IDUs in Northern Vietnam was closely related to those found in Pingxiang city in Guangxi Province of China, sharing a unique valine substitution at 12 amino acids downstream of the V3 loop. The data indicated that HIV outbreaks among IDUs in northern Vietnam were caused by the recent introduction of a highly homogeneous CRF01_AE variant (Ev-variant) that shared the origin with those prevailing in nearby Southern China.2)High prevalence of HIV-1 unique recombinant forms in Myanmar:We found that 10-30% of HIV-1 strains circulating in Myanmar were diverse forms of HIV-1 intersubtype recombinants, comprised of various combinations of three HIV-1 strains, including HIV-1 subtypes B' (Thailand variant of sub … More type B) and C and CRF01_AE, circulating in Myanmar. The results suggest the presence of highly exposed population and social networks in this particular area in Asia.3)Geographical hotspot of extensive HIV-1 intersubtype recombination in Yunnan province of China:Yunnan Province is thought to be an epicenter of explosive HIV-1 epidemic in China. We identified the unique geographical site in western part of Yunnan Province where approximately 2/3 of circulating strains were HIV-1 unique recombinant forms (URFs). We also found new class of HIV-1 recombinants comprised of two previously established circulating recombinant forms in China (CRF07_BC and CRF08_BC). The results suggest that mixing of different HIV-1 strains could quickly generate various forms of recombinants. This may further complicate the development of efficacious vaccine to control the epidemic in this particular area in Asia.(B)Study on host genetic factors influencing the susceptibility to HIV-1 and disease progression in Thai population (Dr. Shioda):Cross-section study using discordant couples in Thailand revealed that CCR5 927T mutation is an important genetic predisposition related to resistance to HIV-1 infection in Thai population. The study based on cohort in northern Thailand demonstrated the linkage between 1L4-589T homozygosity and slower disease progression in female population and the patients under HAART.(C)Immunological study for future vaccine strategies in Asia (Drs. Takiguchi and Yasutomi):Dr. Takiguchi's group characterized the cytotoxic T-cell recognition of HIV-1 cross-clade and clade-specific epitopes in HIV-1 subtype B and CRF01_AE-infected Thai and Japanese patients. Dr. Yasutomi and his colleagues developed novel orally-available vaccine vehicle based on virus-like particle (VLP) from hepatitis E virus that allow to incorporate DNA vaccine constructs and elicit humoral and cytotoxic T cell responses. Less