1999 Fiscal Year Final Research Report Summary
Epidemiological and virological studies of the novel JC virus regulatory regions found in PML patients
| Project/Area Number |
10670281
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOGO Yoshiaki The Institute of Medical Science The University of Tokyo, Associate Professor, 医科学研究所, 助教授 (60092376)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Kazuya School of Allied Sciences, Kitasato University, Assistant professor, 医療衛生学部, 助手 (60164993)
KITAMURA Tadaichi Graduate School of Medicine, The University of Tokyo, Professor, 医学部・附属病院, 教授 (70010551)
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| Project Period (FY) |
1998 – 1999
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| Keywords | JC virus / PML / PCR diagnosis / regulatory region / sequence rearrangement / CSF / central nervous system |
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| Research Abstract |
We established a nested PCR that amplifies the regulatory region of JC virus (JCV) DNA. Using this system, we detected JCV DNA from cerebrospinal fluid (CSF) samples from 19 patients strongly suspected of progressive multifocal leukoencephalopathy (PML). In one case, JCV DNA was detected until 5 months after the onset of PML, but was not detected between 5 and 11 months. The clinical symptoms of the patient appeared to be stabilized. In another case, JCV DNA was detected at high efficiencies in 2 and 3 months after the onset of PML, but was detected in 4 months only at a low frequency. The follow-up of this patient will be performed.
The structures of JCV regulatory regions detected varied markedly. The 'typical ' regulatory regions in which domain A is deleted and domain B is duplicated accounted only for a fourth or third of the total regulatory regions detected. Some regulatory regions underwent more than two steps of rearrangements and some contained only deletions.
We analyzed JCV regulatory regions in autopsy brains and other organs from PML patients. In one case, it was suggested that peripheral lymphocytes were preferentially infected with a JCV variant that carried one of the several rearranged regulatory regions in the brain. In another case, dual origins of JCV infection in the central nervous system were suggested.
We reported that archetype JCV can efficiently replicate in COS-7, simian cells expressing SV40 T antigen. In this study, we examined the growth capacity of various PML-type JCVs in COS-7 cells. Some of the examined PML-type JCVs grew as efficiently as a representative archetype JCV (CY), whereas some replicated more slowly than CY. These data suggested that PML-type regulatory regions are variable in the capacity to enhance viral growth.
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[Publications] Hara. K., Sugimoto, C., Kitamura, T., Aoki, N., Taguchi, F., and Yogo, Y.: "Archetype JC virus efficiently replicates in COS-7 cells, simian cells constitutively expressing simian virus 40 T antigen."J. Virol.. 72. 5335-5342 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Sugimoto, C., Ito, D., Tanaka, K., Matsuda, H., Saito, H., Sakai, H., Fujihara, K., Itoyama, Y., Yamada. T., Kira, J., Matsumoto, R., Mori, M., Nagashima, K., and Yogo, Y.: "Amplification of JC virus regulatory DNA sequences from cerebrospinal fluid : diagnostic value for progressive multifocal leukoencephalopathy."Arch. Virol.. 143. 249-262 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Wakutani, Y., Shimizu, Y., Miura, H., Nakashima, K., Nakano, T., Ohma, E., Sugimoto, C., Yogo, Y., Kobayashi, Y., and Nagashima, K.: "A case of brain-biopsy proven progressive multifocal leukoencephalopathy : pathological findings and analysis of JC virus regulatory region."Neuropathology. 18. 347-351 (1998)
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「研究成果報告書概要(欧文)」より
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