| Project/Area Number |
04454204
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCES |
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Principal Investigator |
YASUI Kotaro Tokyo Metoropolitan Institute for Neurosciences, 微生物学・免疫学・総合研究所・研究部門, 参事研究員 (90073080)
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| Co-Investigator(Kenkyū-buntansha) |
SUGAMATA Masami Tokyo Metoropolitan Institute for Neurosciences, 微生物学・免疫学, 流動研究員 (00091041)
MIYAMOTO Michiko Tokyo Metoropolitan Institute for Neurosciences, 微生物学・免疫学, 主任 (40190821)
KIMURA-KURODA Junko Tokyo Metoropolitan Institute for Neurosciences, 微生物学・免疫学, 主任 (20142151)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1992: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Japanese encephalitis virus / neurovirulence / neuron / cellular receptor / E protein / prM protein / エンベロープ / E-Mヘテロ2量体 / E蛋白のホモ3量体 / レセプター分子 / 感受性 / 細胞受容体 / M蛋白 / preM蛋白 / E蛋白構造 |
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| Research Abstract |
Factors which participated in the pathogenicity of Japanese encephalitis virus were analyzed.
The following results were obtained using primary rat brain culture and established cell lines. 1. Japanese encephalitis virus could infect and replicate in neurons but not in glial cells. 2. Japanese encephalitis virus could be adsorbed and replicate on immature neurons but not on differentiated mature neurons which completed synapse formation. 3. Japanese encephalitis virus could be adsorbed and internalized effectively on susceptible cells but not on unsusceptible cells. 4. Japanese encephalitis virus could replicate in unsusceptible cells which were received the infectious RNA directly into the cytoplasm. 5. A candidate 75Kd receptor molecule which could bind with the E protein of Japanese encephalitis virus was detected and isolated from membrane fractions of susceptible cells.
The following results were obtained from an analysis on the mechanism of particle formation of Japanese encephalit
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is virus. 1. A prM-E heterodimer on an envelope was formed after expression and processing of polyprotein in ER lumen and the prM protein was processed in golgi complex and then the M-E heterodimer on the envelope was released from infected cells as a mature virion. 2. The M-E heterodimer was converted to E homotrimer under low pH conditions. 3. This structural change occurred on the E protein could induce a fusion between the envelope of the virion and cell membranes of susceptible cells after the virion and the cellular receptor binding was completed. 4. The C terminal part of prM protein had essential Hole for the formation of the prM-E heterodimer and the construction of the E protein structure and the transport of the E protein in the cells. 5. Amino acid replacements at the neutralizing epitope induced decreased neurovirulence on the virus.
These results indicate that a part of neurovirulence of Japanese encephalitis virus is determined the binding efficiency between the cellular receptor on the susceptible cells and the E protein of the virion and prM protein has a critical role on the construction of the E protein structure responsible on the reactivity with the receptor and the cell membranes. Less
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