The analysis for the HCV propagation strategy from the infected cells to uninfected cells
Project/Area Number |
20K16267
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 49060:Virology-related
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Research Institution | National Institute of Infectious Diseases (2021-2022) Tokyo University of Science (2020) |
Principal Investigator |
Ohashi Hirofumi 国立感染症研究所, 治療薬・ワクチン開発研究センター, 研究員 (40866761)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | HCV / Lipid droplets / 脂肪滴 / ウイルス伝播 / JFH1 / J6/JFH1 / cell-to-cell / cell free / infection |
Outline of Research at the Start |
C型肝炎ウイルス(HCV)は非感染細胞へ伝播する際にcell freeおよび cell-to-cellの2経路を利用する。これらの経路はHCVが慢性感染を成立・維持させるのに重要と考えられている。しかしながら、細胞内の感染性子孫HCV粒子がどちらの経路を選択して伝播するかのバランスを制御する分子機構は明らかではない。これまでに、HCVは配列に依存してウイルス産生能が異なることが知られる他、申請者は細胞内環境がcell-to-cell伝播の効率を変化させる予備結果を得ている。本研究ではこれらの知見と予備結果を踏まえて、HCVの伝播におけるcell freeおよびcell-to-cell経路選択バランス制御の分子機構を明らかにする。
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Outline of Final Research Achievements |
Hepatitis C virus (HCV) uses cell-free and cell-to-cell transmission pathways to spread progeny viruses to uninfected cells. However, the control machinery for these transmission pathways is unclear. This study revealed that the production of lipid droplets in the infected cells is important for cell-to-cell pathway dependent viral transmission. Additionally, the laboratory HCV strain, Jc1-n, had a higher ability to release progeny viruses as compared to the clinically isolated strain, JFH-1. These data suggest that increased LD formation is important for cell-to-cell transmission and that the strategy of viral spread is also different between HCV strains.
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Academic Significance and Societal Importance of the Research Achievements |
HCVの伝播において、cell-to-cell経路は中和抗体からの回避に重要と考えられているが、この経路に関わる宿主細胞機能は未解明であった。本研究により、HCVのcell-to-cell伝播には宿主細胞の脂肪滴産生が重要であることを明らかとした。本研究で得られた知見により、HCVの伝播機構に関する理解を深めることができた。また、cell-to-cell経路に関与する宿主機能の発見は、この経路を標的とした新たな抗ウイルス化合物探索につながると期待される。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Estimation of the incubation period of COVID-19 using viral load data.2021
Author(s)
Ejima K, Kim KS, Ludema C, Bento AI, Iwanami S, Fujita Y, Ohashi H, Koizumi Y, Watashi K, Aihara K, Nishiura H, Iwami S.
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Journal Title
Epidemics.
Volume: 35
Pages: 100454-100454
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mefloquine, a Potent anti-Severe Acute Respiratory Syndrome- related Coronavirus 2 (SARS-CoV-2) drug as an entry inhibitor in vitro2021
Author(s)
Kaho Shionoya, Masako Yamasaki, View ORCID ProfileShoya Iwanami, Yusuke Ito, Shuetsu Fukushi, Hirofumi Ohashi, Wakana Saso, Tomohiro Tanaka, Shin Aoki, Kouji Kuramochi, Shingo Iwami, Yoshimasa Takahashi, Tadaki Suzuki, Masamichi Muramatsu, Makoto Takeda, Takaji Wakita, Koichi Watashi
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Journal Title
Frontiers in Microbiology
Volume: 1
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Should a viral genome stay in the host cell or leave? A quantitative dynamics study of how hepatitis C virus deals with this dilemma2020
Author(s)
S. Iwanami, K. Kitagawa, H. Ohashi, Y. Asai, K. Shionoya, W. Saso, K. Nishioka, H. Inaba, S. Nakaoka, T. Wakita, O. Diekmann, S. Iwami and K. Watashi
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Journal Title
PLoS Biology
Volume: 18(7)
Issue: 7
Pages: 3000562-3000562
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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