| Project/Area Number |
07044212
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Virology
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| Research Institution | Hokkaido University |
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Principal Investigator |
IKUTA Kazuyoshi Section of Serology, Institute of Immunological Science, Hokkaido University, Professor, 免疫科学研究所, 教授 (60127181)
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| Co-Investigator(Kenkyū-buntansha) |
KAMEOKA Masanori Department of Biochemistry, Nara Medical University, Instructor, 助手 (60281838)
NAKAYA Takaaki Section of Serology, Institute of Immunological Science, Hokkaido University, In, 免疫科学研究所, 助手 (80271633)
AUWANIT Wattana Department of Immunology, NIH,Healthy Science Research Institute, Senior Researc, Senior Res
LUFTIG Ronald B. Department of Microbiology, Immunology and Parasitology, Louisiana State Univers, Medical Cente, Professor
JONES Ian M. NERC Institute of Virology, Project Leader, Ins, Project Le
JONES Ian M. Natural Environment Research Council, Ins, Project Le
木村 卓郎 北海道大学, 免疫科学研究所, 助教授 (20001737)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | HIV-1 / AIDS / clade B / clade E / apoptosis / Nef / latent infection / Thailand / nef / アンチセンスDNA / アクセサリー遺伝子 / ボルナ病ウイルス / HIV / ワクチン / 遺伝子治療 / 不完全粒子 / pol / vpr |
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| Research Abstract |
Infection with human immunodeficiency virus type 1 (HIV-1) leads to AIDS within about 10 years. There are several features ascribed to the AIDS pathogenesis : 1) clinical staging of the disease is significantly correlated with HIV-1 load, 2) potent antiretroviral drugs produce a dramatic drop in plasma viremia, and 3) the anti-HIV-1 drugs are effective for HIV-1 derived from short-lived productively infected cells, but not so effective for HIV-1 derived from latent reservoirs. We have found that infection by HIV-1 with mutations at accessory genes such as vif, vpr, and/or vpu can establish persistent or latent infection in human T-cell line, MT-4. During serial passage of wild-type HIV-1, similar mutations naturally occurred and established latent infection. In contrast, HIV-1 with mutation at nef did not establish persistent infection, indicating that nef gene is necessary for persistent infection of HIV-1. We also found that soluble Nef protein has a function to reactivate HIV-1 from
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latency. In additon, we have found that HIV-1 virion adsorption can generate effector cells to induce apoptosis in bystander uninfected T-cells. These phenomena seem to be important to understand HIV-1-induced pathogenesis. However, all these results were obatined only by characterization of HIV-1 clade B.On the other hand, the HIV-1 spreading in South Eastern Asia including Thailand is clade E.In this international joint research project, we have further characterized HIV-1 clade E from Thai HIV-1 carriers. The full-length sequence of Thai E HIV-1 was first reported in 1996. The E virus for the sequence was isolated from a 21-year-old Thai man, who was determined to be seropositive for HIV-1 at 1990. However, we found that the polymerase chain reaction with primers prepared according to the reported sequence was difficult to amplify the clade E HIV-1 in most of the blood samples recently collected from HIV-1 clade E-seropositive asymptomatic carriers in Thailand, indicating advanced mutations in currently spreading Thai E HIV-1. We could amplify Thai HIV-1 sequences at nef from four isolates of two clade B-seropositive and two E-seropositive carriers using primers according to clade A sequence. The results showed 6.43% genetic variability between two HIV-1 clade E isolates and -13% genetic variability between clade B and E HIV-1 in Thailand. In fact, 13 murine monoclonal antibodies prepared by immunization with clade B Nef protein did not cross-react with these clade E HIV-1 isolates. On th other hand, we confirmed that apoptosis in bystander T-cells was also observed in the blood T-cells prepared from Thai clade E infected carriers by similar mechanism as we have observed by in vitro studies using clade B HIV- particle adsorption. Less
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