Molecular Mechanism of the neurovirulence of rabies vlrus
| Project/Area Number |
04670272
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KAWAI Akihiko Kyoto University, Faculty of Pharmacentical Sciences, Professor., 薬学部, 教授 (70027332)
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| Co-Investigator(Kenkyū-buntansha) |
MORIMOTO Kinjiro Kyoto Univ., Faculty Pharm.Sci., Assis.Prof., 薬学部, 助手 (80183664)
SAGARA Juniji Kyoto Univ., Faculty.Pharm.Sci., Assis.Prof., 薬学部, 助手 (10225831)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Rabies virus / Neurovirulence / Cell fusion / Neuron-Specifi host factor / Acetylcholine recentor / Fusion protein / Fusion domain / ウイルスの病原性 / ウイルスレセプター / アセチルコリンレセプター / ウイルスの侵入 / ウイルスの臓器特異性 / 病原性 / 神経細胞因子 |
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| Research Abstract |
We studied viral and host cell foctors which are involved in displaying the neurovirulent nature of rabies virus. Results can be clivided into three parts as follows.
(1)Host factor(s) reguired for the pH-independent syniytium formation by rabies virus G protein. Acetylcholine recentor (ACHR) has been suggested to be such a factor that is involved in the early stage of the virus infection into the CNS.We also have assumed that the same factor is involved in the pH-independent cell fusion in the neuroblastoms cell cultures caused by the nwurovinlent type G protein of the rabies virus. We cloned the genes encoding either alpha and beta submit of AChR and expressed them in E.coli. We extracted alph and beta submit proteins from the prokaryote cells and used them for raising antibodies against these proteins in rabbits. Antisera obtained were used for experiments in which we examined whether the antisera could block the rabies virus infection in the neuroblactons cell calture. We obtained positive results as expected.
(2) Studies on the fusion domain of G protein. Point mutants were produced to introduce point mutations into the putative fusion domain, deduced by comparing the amino and seguene of G protein and the fusion protein of other virus including HIV and measles virus, that have pH-independent cell-fusing activity. One of mutants, which has a mutation at position 360, lost the pH-independent cell-fusing activity.
(3) The nature of the street virus. By comparing the nature of the street and fixed strains, we found that the infectivity of the street virus was dependent on the AChR expression of NA cells and was also dependent on the cell fusion under low PH conditions.
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Report
(3 results)
Research Products
(20 results)
