2011 Fiscal Year Final Research Report
Cellular biological examination of relationship between viral and host factors and development of therapeutic strategy PML
| Project/Area Number |
21390111
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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 |
Experimental pathology
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| Research Institution | Hokkaido University |
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Principal Investigator |
SAWA Hirofumi 北海道大学, 人獣共通感染症リサーチセンター, 教授 (30292006)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Shinya 北海道大学, 医学研究科, 教授 (70261287)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 細胞 |
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| Research Abstract |
The human polyomavirus JC virus (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML). The JCV encoded agnoprotein has been shown to act as a viroporin, promoting the release of progeny virions. We demonstrate that the JCV agnoprotein specifically interacts with AP-3. This interaction interrupts AP-3-mediated vesicular trafficking with suppression of the targeting of the protein to the lysosomal degradation pathway, and instead permitting the transport of agnoprotein to the cell surface. The findings demonstrate a unique viral-host factors interaction, and suggest that the viroporins of other viruses may also be highly regulated by specific interactions with host factors. In addition, JCV capsid consists of 72 pentameric capsomeres of a major structural protein VP1. We examined the role of cysteine residues in the VP1 expression by individually mutating the six cysteines. The C80A and C247A VP1 mutants showed greatly decreased Vpl expression. Our results suggest that regions of VP1 including Cys80 and Cys247 is essential for JCV virion assembly. These results may be applicable for development of therapeutic strategy for PML and other viral diseases.
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Research Products
(21 results)
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[Presentation] Cys80 of JC virus capsid protein, VP1 is essential for intrapentamer disulfide bond and pentamer formation2010
Author(s)
Kobayashi S, Suzuki T, Igarashi M, Ohtake N, Nakagawa K, Niikura K, Kimura T, Kasamatsu H, Sawa H
Organizer
10^<th> International Symposium on NeuroVirology
Place of Presentation
Milan, Italy
Year and Date
20101012-16
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