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）越南北方艾滋病毒暴发的分子流行病学：我们调查了最近越南北方注射吸毒者中艾滋病毒暴发的分子性质。我们发现分布在越南北方IDUs中的CRF01_AE菌株与在中国广西凭祥市发现的菌株密切相关，在V3环下游12个氨基酸处共享独特的缬氨酸取代。数据表明，越南北方注射吸毒者中的艾滋病毒爆发是由于最近引入了一种高度同质的CRF 01_AE变体（EV变体），该变体与邻近的中国南方流行的变体具有相同的起源。2）HIV-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10-30%的HIV-1毒株是不同形式的HIV-1亚型间重组体，由三种HIV-1毒株的各种组合组成，包括HIV-1亚型B'（泰国亚型的变异体）， 关于我们 B型）和C型以及CRF 01_AE，在缅甸流行。结果表明，在亚洲这一特定地区存在着高暴露人群和社交网络。3）中国云南省广泛的HIV-1亚型间重组的地理热点：云南省被认为是中国爆发性HIV-1流行的震中。我们确定了云南省西部的独特地理位置，那里大约2/3的流行毒株是HIV-1独特重组形式（URF）。我们还发现了新的一类HIV-1重组体，包括先前在中国建立的两种循环重组形式（CRF07_BC和CRF08_BC）。结果表明，不同HIV-1毒株的混合可以快速产生各种形式的重组体。这可能会使开发有效疫苗以控制亚洲这一特定地区的流行病更加复杂。（B）关于影响泰国人口对HIV-1的易感性和疾病进展的宿主遗传因素的研究（Shioda博士）：利用泰国不一致夫妇进行的横断面研究表明，CCR 5 927 T突变是泰国人口中与抵抗HIV-1感染有关的重要遗传易感性。基于泰国北方队列的研究表明，1 L4 - 589 T纯合性与女性人群和HAART患者的疾病进展较慢有关。（C）亚洲未来疫苗策略的免疫学研究（Takiguchi和Yasutomi博士）：Takiguchi博士的小组描述了HIV-1亚型B和CRF 01_AE感染的泰国和日本患者中HIV-1交叉进化枝和进化枝特异性表位的细胞毒性T细胞识别。Yasutomi博士和他的同事们开发了一种新型的口服疫苗载体，该载体基于来自戊型肝炎病毒的病毒样颗粒（VLP），允许掺入DNA疫苗构建体并引发体液和细胞毒性T细胞反应。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