Functional analysis of intracellular annexins involved in the propagation of hepatitis virus
| Project/Area Number |
17K08857
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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 |
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Principal Investigator |
ABE TAKAYUKI 神戸大学, 医学研究科, 准教授 (90403203)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | C型肝炎ウイルス / アネキシン / タイトジャンクション / 細胞間極性 / 肝炎ウイルス |
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| Outline of Final Research Achievements |
Annexins (ANXs) comprise a family of calcium- and phospholipid-binding proteins and are implicated to involve in not only a numerous of cellular processes but also life-cycle of several viral infections. Here we demonstrate a novel insight of annexin A5 (ANXA5) on the HCV life-cycles. The knockdown of ANXA5 remarkably increased the expression of both HCV proteins and HCV RNA levels in the HCV replicon cells. Using an infectious HCV clones, we confirmed the significant enhancement of HCV propagation in the ANXA5 knockdown cells, suggesting that ANXA5 acts as a negative regulator of HCV infection. Furthermore, the confocal microscopic analysis revealed that ANXA5 is required for the proper cellular localization of tight-junction (TJ) proteins such as CLDN-1 and OCLN, which are critical entry factors for HCV infection. These results provide new insights into the HCV life-cycle on the function of ANXA5 that acts via modulation of TJ proteins assembly.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の主な成果として、肝炎ウイルスに対する新たな増殖抑制因子として、アネキシン5分子を同定したことが挙げられる。また、学術的な新たな知見として、アネキシン5分子がタイトジャンクション形成の恒常性維持にも関与していることを明らかにした。タイトジャンクション形成の恒常性維持の破綻は、癌、難聴、糖尿病などの様々な疾患の要因になることが示唆されている。アネキシン5分子の機能を詳細に解析することで、肝炎ウイルスの排除のみならず、タイトジャンクション形成の恒常性維持の破綻に起因する様々な疾患に対する分子機序、ならびに治療法開発への道が開ける可能性がある。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Peroxiredoxin 1, a novel HBx-interacting protein, interacts with exsome component 5 and negatively regulates hepatitis B virus (HBV) propagation through degradation of HBV RNA.2019
Author(s)
Lin Deng, Xiang Gan, Masahiko Ito, Ming Chen, Hussein H. Aly, Chieko Matsui, Takayuki Abe, Koichi Watashi,Takaji Wakita, Tetsuro Suzuki, Toru Okamoto, Yoshiharu Matsuura, Masashi Mizokami, Ikuo Shoji, and Hak Hotta.
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Journal Title
J. Virol
Volume: 93
Issue: 6
DOI
Related Report
Peer Reviewed / Open Access
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