The study for the persistent infection of cytomegalovirus in the developing cerebral neuron
| Project/Area Number |
18500278
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
KOSUGI Isao Hamamatsu University School of Medicine, School of Medicine, Associate Professor (10252173)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASAKI Hideya Hamamatsu University School of Medicine, School of Medicine, Assistant Professor (90397381)
TSUTSUI Yoshihiro Hamamatsu University School of Medicine, School of Medicine, Professor (50073135)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | cvtomegalovirus / developmental brain disorder / recombinant virus / persistent infection / neuronal disorder / pimary neuronal culturure / サイトロメガロウイルス |
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| Research Abstract |
Cytomegalovirus (CMV) is the leading viral cause of developmental brain disorders in humans. During murine CMV (MCMV) infection of newborn mice, viral early-antigen (El, product of el gene ; M112/113) persisted in neurons of hippocampus (HP) and cerebral cortex (CX) after disappearance of El from non-neuronal cells. Furthermore, neuron-specific activation of MCMV-el promoter (el-pro) in our transgenic mice suggests that a unique el-pro activation likely occurs in developing neurons and may be an important factor for viral neuropathogenesis.
We have constructed recombinant MCMV (rMCMV1373 or rMCMV448), which expresses EGFP as a reporter under control of full-length (1373 nt) or truncated (448 nt) el-pro fragment. We have investigated differences in el-pro activation between neurons and non-neuronal cells, in situ, during rMCMV infection of developing mouse brains and primary neuronal cultures.
Among any brains infected with wild-type MCMV or rMCMVs, at 7 days-post-infection (dpi) viral an
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tigens (IE1, IE3 and E1) were expressed not only in non-neuronal cells of periventricular area (PV) but also in neurons of HP and CX. At 11 dpi antigens disappeared from PV but persisted exclusively in neurons. In rMCMV 1373-infected brains, kinetics of EGFP expression was the same as that of El. While in rMCMV 448-infected brains EGFP was clearly detected in non-neuronal cells until 7dpi, but not in neurons at any time despite the enough neuronal E1 expression. In rMCMV 1373-infected primary neuronal cultures, EGFP was also preferentially detected in neurons, but very scarcely in rMCMV 448-infected neurons.
Our results suggest that IE3-binding sites in truncated el-pro fragment is involved in sufficient el-pro activation in non-neuronal cells as reported previously. However, upstream region from -449 to -1373 nt in full-length el-pro fragment seems to be necessary for neuron-specific activation of el-pro. It is supposed that this unique neuronal el-pro activation may be closely associated with viral neurotropism and neuropathogenesis. Less
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Report
(3 results)
Research Products
(31 results)
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[Journal Article] Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide : a model for hearing loss in congenital CMV infection(in press)2008
Author(s)
Li, L, Kosugi, I., Han, GP, Kawasaki, H., Arai, Y., Takeshita, T., Tsutsui, Y
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「研究成果報告書概要(欧文)」より
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[Journal Article] Roles of neural stem progenitor cells in cytomegalovirus infection of the brain in mouse models(in press)2008
Author(s)
Tsutsui, Y., Kosugi, I., Kawasaki, H., Arai, Y., Han, G-P, Li, L., Kaneta, M
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Journal Title
Pathology International 58
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Enhancement of susceptibility of adult mouse brain to cytomegalovirus infection by infusion of epidermal growth factor2007
Author(s)
Han, GP, Li, L., Kosugi, I., Kawasaki, H., Tsuchida, T., Miura, K., Tsutsui, Y
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Journal Title
Journal of Neuroscience Research 85(13)
Pages: 2981-2990
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Differential expression of the immediate-early 2 and 3 proteins in developing mouse brains infected with murine cytomegalovirus2006
Author(s)
Ishiwata, M., Baba, S., Kawashima, M., Kosugi, Kawasaki, H., Kaneta, M., Tsuchida, T., Kozuma, S., Tsutsui, Y
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Journal Title
Archives of Virology 151(11)
Pages: 2181-2196
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mouse embryonic stem cells are not susceptible to cytomegalovirus but acquire susceptibility during differentiation2006
Author(s)
Matsukage, S., Kosugi, I., Kawasaski, H., Miura, K., Kitani, H., Tsutsui, Y
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Journal Title
Birth Defects Research (Part A) 76
Pages: 115-125
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Latent cytomegalovirus infection in neural stem cells of developing mouse brain2007
Author(s)
Tsutsui, Y., Suzuki, H., Han, GP., Li, L., Kawasaki, H., Kosugi, I
Organizer
The 11th International Cytomegalovirus/ Betaherpes Virus Workshop, Pierre Baudis Congress Center
Place of Presentation
Toulouse, France
Description
「研究成果報告書概要(欧文)」より
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