Mechanistic analysis of post-traslational modification of viral RNA and its anti-viral application
| Project/Area Number |
18F18098
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Research Field |
Virology
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
アリ フセインハッサン 国立感染症研究所, ウイルス第二部, 主任研究官 (00523515)
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| Co-Investigator(Kenkyū-buntansha) |
IBRAHIM MARWA 国立感染症研究所, ウイルス第二部第三室, 外国人特別研究員
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| Project Period (FY) |
2018-10-12 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2020: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2019: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2018: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | HBV / pgRNA / MafF / RNA degradation / IL-1b / HBV-pgRNA / HBV-RNA / Degradation / virus host interaction / Transcription |
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| Outline of Annual Research Achievements |
Hepatitis B Virus (HBV) is a stealth virus that exhibits only minimal induction of the interferon system that is required for both innate and adaptive immune responses. However, 90% of acutely infected adults can clear the virus, suggesting the presence of additional mechanisms that facilitate viral clearance. Marwa identified Maf bZIP transcription factor F (MafF) to promote host defense against infection with HBV. MafF was found to control HBV-pgRNA levels. Her data showed that silencing of MafF led to 6-fold increase in luciferase activity after HBV/NL infection, induced HBV-pgRNA levels, HBV replication, and the expression of HBV core protein expressed from HBV-pgRNA. Overexpression of MafF reduced HBV core promoter transcriptional activity, which was relieved upon mutating the putative MafF binding region. Marwa found that MafF is induced by famous inflammatory cytokines IL-1b and TNF-a. Analyzing the data from human hepatocytes chimeric mouse infected in-vivo with HBV, or single cell data from primary hepatocytes infected in-vitro with HBV; she found that MafF levels were induced after HBV infection, confirming the induction of MafF levels in response to HBV infection. The anti-viral effect of MafF was also extended to EBV, where MAfF suppressed genes required for activation of EBV infection (BZLF1 gene).
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| Research Progress Status |
令和2年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和2年度が最終年度であるため、記入しない。
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Report
(3 results)
Research Products
(18 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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[Journal Article] Interferon sensitivity-determining region of hepatitis C virus influences virus production and interferon signaling2017
Author(s)
Sugiyama R., Murayama A., Nitta S., Yamada N., Tasaka-Fujita M., Masaki T., Aly H. H., Shiina M., Ryo A., Ishii K., Wakita T. and Kato T.
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Journal Title
Oncotarget
Volume: 9
Issue: 5
Pages: 5627-5640
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] MafF is a novel host restriction factor for HBV which suppresses transcription from HBV-core promoter2020
Author(s)
Marwa K. Ibrahim1,2, Yingfang Li, Tawfeek A Hussein, Koichi Watashi, Takanobu Kato, Asako Murayama, Tetsuro Suzuki, Kunitada Shimotohno, Kazuaki Chayama, Takaji Wakita, Masamichi Muramatsu, Hussein H Aly
Organizer
American Society of Virology (online)
Related Report
Int'l Joint Research
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[Presentation] MafF is a key player of IL-1β-induced suppression of transcription from HBV-core promoter, and the resulting suppression of viral replication.2019
Author(s)
2.Marwa K. Ibrahim, Sameh A. Gad, Koichi Watashi, Li Yingfang, Masaya Sugiyama, Masahiko Ito, Asako Murayama, Tetsuro Suzuki, Takanobu Kato, Kunitada Shimotohno, Masamichi Muramatsu, Takaji Wakita, Hussein H. Aly.
Organizer
2019 International Meeting, molecular Biology of Hepatitis B virus. Oral presentation,
Related Report
Int'l Joint Research
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[Presentation] Marwa Khalil Ibrahim, Sameh A Gad, Koichi Watashi, Takanobu Kato, Asako Murayama, Kunitada Shimotohno, Takaji Wakita, Masamichi Muramatsu, Hussein Aly2019
Author(s)
MAFF IS AN IMPORTANT REGULATOR OF HBV CORE PROMOTER ACTIVITY, AND HBV REPLICATION
Organizer
The Liver Meeting 2019, The 70th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
Related Report
Int'l Joint Research
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[Presentation] The IL-1 β induced (MafF) is an important regulator of HBV core promoter activity.2019
Author(s)
1.Marwa K. Ibrahim, Sameh A. Gad, Koichi Watashi, Li Yingfang, Masaya Sugiyama, Masahiko Ito, Asako Murayama, Tetsuro Suzuki, Takanobu Kato, Kunitada Shimotohno, Masamichi Muramatsu, Takaji Wakita, Hussein H. Aly.
Organizer
The 67th Annual Meeting of the Japanese Society for Virology. Tokyo
Related Report
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[Presentation] Establishment of Infectious Genotype 4a Hcvcc.2018
Author(s)
3.Noriyuki Watanabe, Takaya Suzuki, Tomoko Date, Su Su Hmwe, Hussein Aly, Hideki Aizaki, Masaya Sugiyama, Masashi Mizokami, Mohamed El Kassas, Ashraf Tabll, Guofeng Cheng, William E Delaney, Masamichi Muramatsu, Takaji Wakita
Organizer
American Asspciation for the Study of Liver Diseases AASLD, San Francisco,
Related Report
Int'l Joint Research / Invited
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