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

亚洲HIV分子流行病学及影响疾病进展的宿主因素研究

• 批准号: 13376002
• 负责人: TAKEBE Yutaka
• 金额: $ 13.4万
• 依托单位: NATIONAL INSTITUTE OF INFECTIOUS DISEASES
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13376002/
• 关键词: Asia; AIDS; HIV; molecular epidemiology; HIV-1 subtypes; HIV-1 recombinants; genetic polyorphism; host factors; CTLエピトープ; ケモカイン受容体; 経口ワクチンベクター; CCR2

(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

(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（IDU）近期艾滋病毒暴发的分子性质。我们发现分布在越南北部注射吸毒者中的CRF01_AE菌株与中国广西省凭祥市发现的菌株密切相关，在V3环下游的12个氨基酸上有一个独特的缬氨酸取代。数据表明，越南北部注射吸毒者中艾滋病毒的爆发是由最近引入的高度同质的 CRF01_AE 变体（Ev 变体）引起的，该变体与中国南部附近流行的病毒同源。 2）缅甸 HIV-1 独特重组形式的高流行：我们发现在缅甸传播的 HIV-1 毒株中有 10-30% 是多种形式的 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'（B 亚型的泰国变体）和 C 以及 CRF01_AE，在缅甸流行。结果表明，亚洲这一特定地区存在高度暴露的人群和社会网络。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HIV-1爆发性流行的中心。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)。我们还发现了新一类 HIV-1 重组体，由两种先前在中国建立的循环重组体（CRF07_BC 和 CRF08_BC）组成。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的疫苗来控制亚洲这一特定地区的流行病进一步复杂化。(B)影响泰国人群对 HIV-1 易感性和疾病进展的宿主遗传因素的研究（Shioda 博士）：使用泰国不一致夫妇进行的横断面研究表明，CCR5 927T 突变是泰国人群中与抵抗 HIV-1 感染相关的重要遗传易感性。基于泰国北部队列的研究证明了 1L4-589T 纯合性与女性群体和接受 HAART 治疗的患者中疾病进展较慢之间的联系。(C)亚洲未来疫苗策略的免疫学研究（Takiguchi 博士和 Yasutomi）：Dr. Takiguchi 的研究小组对 HIV-1 B 亚型和 CRF01_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 细胞识别进行了表征。 Yasutomi 博士和他的同事开发了一种基于戊型肝炎病毒的病毒样颗粒 (VLP) 的新型口服疫苗载体，该载体可以掺入 DNA 疫苗结构并引发体液和细胞毒性 T 细胞反应。较少的

项目成果

Motomura, K., et al.: "Different subtype distribution in the two cities in Myanmar : Evidence for independent clusters of HIV-1 transmission."AIDS. 17(4). 14-17 (2003)

Motomura, K. 等人：“缅甸两个城市的不同亚型分布：HIV-1 传播独立集群的证据。”艾滋病。

Takebe, Y., Kusagawa, S., Motomura, K.: "Moleucular epidemiology of HIV : Tracking AIDS Pandemie."Pediatric International. (in press). (2004)

Takebe, Y.、Kusakawa, S.、Motomura, K.：“HIV 分子流行病学：追踪艾滋病大流行。”儿科国际。

Kato, K., Kusagawa, S, Motomura, K, Takebe, Y., et al.: "Closely related HIV-1 CRF01_AE variants among injecting drug users in northern Vietnam : Evidence of HIV spread across the Vietnam-China border"AIDS Res. and Hum. Retroviruses. 17. 113-123 (2001)

Kato, K.、Kusakawa, S、Motomura, K、Takebe, Y.等人：“越南北部注射吸毒者中密切相关的 HIV-1 CRF01_AE 变体：HIV 跨越越南-中国边境传播的证据”艾滋病

Kusagawa, S., Takebe, Y., Yang R., Motomura K., Ampofo, W., Nagai, Y., Ttsumi, M., et al.: "Isolation and characterization on full-length molecular DNA clones of Ghanaian HIV-1intersubtype A/G recombinant(CRFO2-AG)which is replication-competent in restric

Kusakawa, S.、Takebe, Y.、Yang R.、Motomura K.、Ampofo, W.、Nagai, Y.、Ttsumi, M. 等人：“加纳全长分子 DNA 克隆的分离和表征

Yang, R., Xia, X., Kusagawa, S., Zhang, C., Ben, K., Takebe, Y.: "On-going generation of multiple forms of HIV-1 intersubtype recombinants in Yunnan province of China"AIDS. (accepted).

Yang, R.、Xia, X.、Kusakawa, S.、Zhang, C.、Ben, K.、Takebe, Y.：“中国云南省正在产生多种形式的 HIV-1 亚型间重组体”