2005 Fiscal Year Final Research Report Summary
Investigation of tissue destruction signals on viral encephalitis
| Project/Area Number |
16390112
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kyoto University |
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Principal Investigator |
KOYANAGI Yoshio Kyoto University, Institutes for Virus Research, Professor, ウイルス研究所, 教授 (80215417)
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| Project Period (FY) |
2004 – 2005
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| Keywords | HIV / HSV / Encephalitis / Brain / hippocampal slice culture / Neuronal differentiation / Macrophage / Microaray |
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| Research Abstract |
To solve the pathological mechanism of HIV and HSV encephalitis, especially regarding the tissue destruction signals in brain, we established a rat hippocampal slice culture in which histological neuronal structure is maintained and examined the dynamics of virus replication in this culture. Although massive dissemination of HSV-1 infection and severe tissue damage was found, the virus is able to reside in and be produced from some immature cells, probably neuronal stem cells, suggesting that neuronal stem cell is one of the major targets for persistent and active infection in brain tissues. Macrophages appear to be one of the key cell types that are infected by HIV-1 within brain tissue. It has been shown that macrophages infected with HIV-1 invade to brain and release some factors which provide damage to neurons. Although the slice culture was not susceptible to HIV-1, culture condition of some neurons and differentiation ability of neuronal progenitors appeared to be significantly disturbed in the presence of HIV-1-infected human macrophages, probably which may produce neurotoxic factors and neuronal differentiation inhibition factor. Then, both HSV-1- and HIV-1-infected samples were applied for microarray analysis to find specific signal molecules influencing viral pathogenesis. So far, many candidate cellular molecules were found and the alternations of its expression were confirmed from RNA-PCR analysis. These data suggest that brain-derived host factors contribute to augmentation of virus pathogenesis in CNS.
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Research Products
(22 results)
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[Journal Article] Anti-V3 humanized antibody KD-247 effectively suppresses ex vivo generation of human immunodeficiency virus type 1 and affords sterile protection of monkeys against a heterologous simian/human immunodeficiency virus infection.2006
Author(s)
Eda Y, Murakami T, Ami Y, Nakasone T, Takizawa M, Someya K, Kaizu M, Izumi Y, Yoshino N, Matsushita S, Higuchi H, Matsui H, Shinohara K, Takeuchi H, Koyanagi Y, Yamamoto N, Honda M.
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Journal Title
J.Virol. 80
Pages: 5563-5570
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Potent Anti-R5-human immunodeficiency virus type 1 effects of a CCR5 antagonist, AK602/ON04128/GW873140, in a novel human peripheral blood mononuclear cell nonobese diabetic-SCID, interleukin 2 receptor γ-chain-knocked-out AIDS mouse model.2005
Author(s)
Nakata H, Maeda K, Miyakawa T, Shibayama S, Matsuo M, Takaoka Y, Ito M, Koyanagi Y, Mtsuya H.
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Journal Title
J.Virol. 79
Pages: 2087-2096
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Th1/Th2 balance and HTLV-I proviral load in HAM/TSP patients treated with interferon-β2004
Author(s)
Feng J, Misu T, Fujihara K, Misawa N, Koyanagi Y, Shiga Y, Takeda A, Sato S, Takase S, Kohnosu T, Saito H, Itoyama Y.
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Journal Title
J Neuroimmunol. 51
Pages: 189-194
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-Chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro.2004
Author(s)
Maeda K, Nakata H, Koh Y, Miyakawa T, Ogata H, Takaoka Y, Shibayama S, Sagawa K, Fukushima D, Moravek J, Koyanagi Y, Mitsuya H.
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Journal Title
J.Virol. 78
Pages: 8654-8662
Description
「研究成果報告書概要(欧文)」より
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