Progressive multifocal leukoencephalopathy: Dynamics of PML-NBs of JC virus-infected glial cells
| Project/Area Number |
15K06759
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
Hara Yukiko 東京医科大学, 医学部, 准教授 (40313267)
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| Co-Investigator(Kenkyū-buntansha) |
菅間 博 杏林大学, 医学部, 教授 (10195191)
矢澤 卓也 獨協医科大学, 医学部, 教授 (50251054)
千葉 知宏 杏林大学, 医学部, 講師 (60398617)
矢澤 華子 (佐藤 / 佐藤 華子) 獨協医科大学, 医学部, 講師 (60438132)
石井 順 獨協医科大学, 医学部, 助教 (80749599)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 進行性多巣性白質脳症 / JC virus / PML-NBs / 脱髄 / 細胞周期 / 転写因子 / 細胞変性 / JCウイルス / PML-NBｓ / 腫瘍抑制 / agnoprotein |
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| Outline of Final Research Achievements |
Progressive multi focal leukoencephalopathy (PML) is a demyelinating disorder caused due to JCV infection. Previous studies demonstrated that JCV capsid proteins accumulate to the promyelocytic leukemia nuclear bodies (PML-NBs), where they are assembled into virions. To clarify functions of PML-NBs, we expressed JCV capsid proteins, VP1 and VP2/VP3 in the presence or absence of agnoprotein, and assembly of virus-like particles (VLPs) was examined. The results indicated that (1) JCV efficiently produces VLPs, in the presence of agnoprotein, with regulated expression levels of capsid proteins. (2) Overexpression of the capsid proteins, in the absence of agnoprotein, results in ectopic assembly of irregular VLPs. (3) Moreover, mRNA expression levels of transcription factors increased in presence of agnoprotein. Thus, it may be indicated that the levels of transcription factors, which are important for JCV reproduction would be increased, when capsid assembly occurs at PML-NBs.
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| Academic Significance and Societal Importance of the Research Achievements |
PML-NBsは広く真核細胞の核内にみられる構造であるが、その機能は多彩である。ウイルス感染においてはウイルス遺伝子の転写や、ウイルス粒子形成の場として研究されているが、JCV感染でPML-NBsの解析を積極的に行っている研究は、世界的に少数である。希少研究である上に、培養細胞と人体組織を関連させたtranslational researchが行われているという点で、本研究は学術的意義が高い。また、近年、免疫抑制剤などの使用に伴うJCV再活性化、PML発症が問題となっている。JCV溶解感染のメカニズムを明らかにすれば、将来的には薬剤関連PMLの対策にも貢献できる可能性がある。
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Report
(5 results)
Research Products
(14 results)
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[Journal Article] Fingolimod-associated PML with mild IRIS in MS2017
Author(s)
Nishiyama Shuhei、Misu Tatsuro、Shishido-Hara Yukiko、Nakamichi Kazuo、Saijo Masayuki、Takai Yoshiki、Takei Kentarou、Yamamoto Naoki、Kuroda Hiroshi、Saito Ryuta、Watanabe Mika、Tominaga Teiji、Nakashima Ichiro、Fujihara Kazuo、Aoki Masashi
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Journal Title
Neurology - Neuroimmunology Neuroinflammation
Volume: 5
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Progressive Multifocal Leukoencephalopathy with Balanced CD4/CD8 T-Cell Infiltration and Good Response to Mefloquine Treatment2016
Author(s)
Sanjo N, Kina S, Shishido-Hara Y, Nose Y, Ishibashi S, Fukuda T, Maehara K, Eishi Y, Mizusawa H, Yokota T
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Journal Title
Internal Medicine
Volume: 55
Issue: 12
Pages: 1631-1635
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed / Open Access
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