| Project/Area Number |
15300112
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Hokkaido University |
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Principal Investigator |
SAWA Hirofumi Hokkaido University, Research Center for Zoonosis Control, Dept. of Molecular Pathobiology, Professor, 人獣共通感染症リサーチセンター, 教授 (30292006)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hidehiro National Institute of Infectious Diseases, Department of Pathology, Section Chief, 感染病理部, 室長 (70260271)
MOTOYAMA Noboru National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Department of Geriatric Research, Section Chief, 研究所・老年病研究部, 室長 (50277282)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | JC virus / Agnoprotein / siRNA / JC virus / Agnoprotein(Agno) / agnoprotein / 感染抑制 |
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| Research Abstract |
In this project, we have attempted to inhibit JC virus (JCV) infection using small interfering RNAs (siRNAs) against JCV agnoprotein (Agno) as therapeutic strategy. In order to inhibit JCV infection in infected cells, we synthesized double-stranded siRNAs which are specific for JCV coding protein, Agno and introduced these into infected human glial-derived cells. We have observed that in post-infection treatment with siRNAs targeting JCV Agno suppresses virus production in JCV infected cells. Based on the results, we applied two patents and established the paper (J Virol 78: 7270, 2004). In addition, we have established JCV infection mimicking model using mice which were intracerebrally inoculated JCVinfected cells, and applied siRNA against JCV Agno to the model in vivo. After treatment with the siRNA, the number of intracerebral JCVinfected cells was significantly decreased. In addition, we have found that clinical drug was effectively suppressed JCV infection by modification of phosphorylation of a protein in vitro. In the future, the drug might be applicable for the JCV infected progressive multifocal leukoencephalopathy cases. We also examined the mechanism of intracellular translocation of JCV virion using the yeast two-hybrid assay using JCV Agno as a bait. We identified two cellular proteins as Agno-binding proteins. These proteins played a pivotal role in nuclear egress of JCV virion. These results were established (EMBO Rep 6: 452, 2005 and J Biol Chem 280, 24948, 2005). We also established some articles concerning about interaction between viral infection and host response.
10. KEYWORDS
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