1998 Fiscal Year Final Research Report Summary
Pathogenesis and Control of AIDS
| Project/Area Number |
07277101
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAGAI Yoshiyuki Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (20022874)
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| Co-Investigator(Kenkyū-buntansha) |
HAYAMI Masanori Institute for Virus Research, Kyoto University, Professor, ウイルス研究所, 教授 (40072946)
UCHIYAMA Takashi Graduate School of Medicine, Kyoto University, Professor, 大学院・医学研究科, 教授 (80151900)
ADACHI Akio School of Medicine, University of Tokushima, Professor, 医学部, 教授 (90127043)
YAMAMOTO Naoki School of Medicine, Tokyo Medical and Dental University, Professor, 医学部, 教授 (00094053)
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| Project Period (FY) |
1995 – 1997
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| Keywords | HIV replication / AIDS pathogenesis / Viral genome / host factors / Human genome / anti HIV response / animal model / antiviral drugs |
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| Research Abstract |
This project aimed to understand the mechanism of HIV replication in cells, model animals and humans, clarify the nature of host response to HIV infection and develop strategies for controlling HIV infection and AIDS pathogenesis. Over 80 researchers participated in this project, which comprised of five subthemes ; 1) Mechanism of HIV replication, 2) Virological basis of pathogenesis, 3) Immunological basis of pathogenesis, 4) Development of animal models and 5) Control of infection and pathogenesis. Their researches in three years period were able to reveal novel features of interactions of viral proteins with cellular components in HIV life cycle and identify viral genome changes, host proteins and genetic polymorphism that were likely specific for or associated with disease progression. Outcomes of the research also included the identification cytotoxic T cell epitopes crucial for antiviral state and development of animal models such as the trasgenic and SCID/hu mice and the monkey model, which allowed evaluation of HIV infection and pathogenesis. Efforts were also made to design and develop therapeutic compounds for AIDS. Several novel candidate compounds of high potential were created. These outcomes represent a significant contribution to the understanding and control of HIV/AIDS pathogenesis. Important research topics in future are further clarification of genetic and immunological background underlying susceptibility/resistance and disease progression by analyzing high risk/uninfected populations as well as long term nonprogressors. It is also important to learn how once destroyed immunological functions would be reconstructed in AIDS patients during highly active antiretroviral therapy.
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[Publications] T. Shioda, H. Kato, Y. Ohnishi, K. Tashito, M. Ikegawa, E. E. Nakayama, H. Hu, A. Kato, Y. Sakai, H. Liu, T. Honjo, A. Nomoto, A. Iwamoto, C. Morimoto and Y. Nagai: "Anti-HIV-1 and chemotactic activities of human SDF-1α and SDF-1β are abolished by CD26/dipeptidyl peptidase IV mediated cleavage"Proc. Natl. Acad. Sci. USA. 95. 6331-6336 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] H. Liu, D. Chao, E. E. Nakayama, H. Taguchi, M. Gotoh, X. Xin, J. Takamatsu, H. Saito, Y. Ishikawa, T. Azaka, T. Juji, Y. Takebe, T. Ohishi, K. Fukutake, Y. Maruyama, S. Yashiki, S. Sonoda, T. Nakumura, Y. Nagai, A. Iwamoto and T. Shioda: "Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression"Proc. Natl. Acad. Sci. USA. (in press).
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「研究成果報告書概要(欧文)」より
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[Publications] T. Murakami, T. Nakajima, Y. Koyanagi, K. Tachibana, N. Fujii, H. Tamamura, N. Yoshida, M. Waki, A. Matsumoto, O. Yoshie, T. Kishimoto, N. Yamamoto and T. Nagasawa: "A small molecule CXCR4 inhibitor that blocks T cell-line tropic HIV-1 infection"J. Exp. Med.. 186. 1389-1393 (1997)
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「研究成果報告書概要(欧文)」より
