Grant-in-Aid for Scientific Research (A)
|Allocation Type||Single-year Grants |
|Research Institution||NATIONAL INSTITUTE OF INFECTIOUS DISEASES |
TAKEBE Yutaka NATIONAL INSTITUTE OF INFECTIOUS DISEASES, AIDS RESEARCH CENTER, CHIEF, エイズ研究センター, 室長 (50126116)
SHIODA Tatsuo OSAKA UNIVERSITY, PROFESSOR, 微研免疫・ウイルス感染制御分野, 教授 (00187329)
SHIINO Teiichirou NATIONAL INSTITUTE OF INFECTIOUS DISEASES, AIDS RESEARCH CENTER, SENIOR RESEARCHER, エイズ研究センター, 主任研究官 (90291129)
SATO Hironori NATIONAL INSTITUTE OF INFECTIOUS DISEASES, DIVISION OF MOLECULAR GENETICS, SENIOR RESEARCHER, 遺伝子解析室, 主任研究官 (80260272)
YASUTOMI Yasuhiro MIE UNIVERSITY, ASSOCIATE PROFESSOR, 医学部・生体防御学医学講座, 助教授 (90281724)
TAKIGUCHI Masafumi KUMAMOTO UNIVERSITY, PROFESSOR, 医学部・エイズ学研究センター, 教授 (00183450)
|Project Period (FY)
2001 – 2003
Completed (Fiscal Year 2003)
|Budget Amount *help
¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000)
Fiscal Year 2003: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2002: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2001: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
|Keywords||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
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