Comprehensive phosphoproteomics analysis of herpesvirus pathogenicity
| Project/Area Number |
24790434
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Virology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KATO Akihisa 東京大学, 医科学研究所, 助教 (40581187)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 単純ヘルペスウイルス / リン酸化プロテオーム解析 / vdUTPase / Us3 / 神経病原性 / 中枢神経系 / リン酸化プロテオーム / カプシド / 軸索輸送 |
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| Outline of Final Research Achievements |
Herpes simplex virus 1 (HSV-1) encodes Us3 protein kinase and a dUTPase (vdUTPase), which are both critical for neurovirulence in the central nerve system (CNS) of mice. We showed that Us3 phosphorylated vdUTPase to up-regulate its enzymatic activity. This phosphorylation was specifically required for neurovirulence in the CNS of mice, but not for pathogenic effects in mouse eyes and vaginas. Low endogenous cellular dUTPase activity in cell cultures and in vivo was linked to lower replication and virulence of a recombinant virus carrying a mutation that precluded phosphorylation of vdUTPase, and overexpression of cellular dUTPase restored HSV-1 neurovirulence in the CNS by the recombinant virus. Our results supported the hypothesis that CNS-specific neurovirulence of HSV-1 involved strict regulation of vdUTPase activity by Us3 phosphorylation, to compensate for the low cellular dUTPase activity in the CNS, to produce efficient viral replication.
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Report
(4 results)
Research Products
(58 results)
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[Journal Article] Interactome analysis of herpes simplex virus 1 envelope glycoprotein H. Hirohata Y, Kato A, Oyama M, Kozuka-Hata H, Koyanagi N, Arii J, Kawaguchi Y.2015
Author(s)
Y. Hirohata, A. Kato, M. Oyama, H. Kozuka-Hata, N. Koyanagi, J. Arii and Y. Kawaguchi.
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Journal Title
Microbiol. Immunol.
Volume: 印刷中
Pages: 331-337
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimuli2014
Author(s)
Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, Nagata K, Kato A, Kawaguchi Y, Sato H, Yoneda M, Kai C, Yada T, Suzuki Y, Yamada T, Ozawa T, Kaneki K, Inoue T, Kobayashi M, Kodama T, Wada Y, Sekimizu K and Akimitsu N.
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Journal Title
Mol. Cell
Volume: 53
Pages: 393-406
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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