Molecular mechanism of HSV cell-to-cell-spread
| Project/Area Number |
17K08851
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Kobe University (2019-2020)
The University of Tokyo (2017-2018) |
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Principal Investigator |
Arii Jun 神戸大学, 医学研究科, 特命准教授 (30704928)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 単純ヘルペスウイルス / 糖タンパク質 / 細胞間伝播 / MEK/ERKシグナル / HSV / ヘルペスウイルス / 細胞内シグナル / ウイルス / ウイルス粒子形成 / 膜タンパク質 / レセプター |
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| Outline of Final Research Achievements |
Herpesviruses are ubiquitous pathogens of various animals, including humans. These viruses primarily pass through cell junctions to spread to uninfected cells. This method of cell-to-cell spread is an important pathogenic characteristic of these viruses. Here, we show that the host cell protein prohibitin-1 contributes to HSV-1 cell-to-cell spread via a downstream intracellular signaling cascade, the MAPK/ERK pathway. We also demonstrate that the role of the prohibitin-1-mediated MAPK/ERK pathway in viral cell-to-cell spread is conserved in representative members of every herpesvirus subfamily. This study has revealed a common molecular mechanism of the cell-to-cell spread of herpesviruses.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトを宿主とするヘルペスウイルスは9種存在するが、その中には抗ウイルス剤がほぼ効果がないものも存在する。本研究が同定したPHB1およびMEK/ERKシグナルは、HSVだけでなく、ヘルペスウイルス科に属する三つの亜科すべてに共通して細胞間伝播を促進していた。すなわち本研究により、MEK/ERKシグナルに対する阻害剤は、すべてのヘルペスウイルス感染症に効果のある新規抗ヘルペスウイルス剤のターゲットとなりうる可能性が、提示できたと考えられる。
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Report
(5 results)
Research Products
(62 results)
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[Journal Article] Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.2018
Author(s)
Sato R, Kato A, Chimura T, Saitoh SI, Shibata T, Murakami Y, Fukui R, Liu K, Zhang Y, Arii J, Sun-Wada GH, Wada Y, Ikenoue T, Barber GN, Manabe T, Kawaguchi Y, Miyake K.
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Journal Title
Nat Immunol.
Volume: 19
Issue: 10
Pages: 1071-1082
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Herpes Simplex Virus 1 VP22 Inhibits AIM2-Dependent Inflammasome Activation to Enable Efficient Viral Replication.2018
Author(s)
Maruzuru Y, Ichinohe T, Sato R, Miyake K, Okano T, Suzuki T, Koshiba T, Koyanagi N, Tsuda S, Watanabe M, Arii J, Kato A, Kawaguchi Y.
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Journal Title
Cell Host Microbe.
Volume: 23
Issue: 2
Pages: 254-265
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis.2017
Author(s)
Koyanagi N, Imai T, Shindo K, Sato A, Fujii W, Ichinohe T, Takemura N, Kakuta S, Uematsu S, Kiyono H, Maruzuru Y, Arii J, Kato A, Kawaguchi Y.
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Journal Title
J Clin Invest.
Volume: 127
Issue: 10
Pages: 3784-3795
DOI
Related Report
Peer Reviewed / Open Access
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