2019 Fiscal Year Annual Research Report
Mechanistic analysis of post-traslational modification of viral RNA and its anti-viral application
| Project/Area Number |
18F18098
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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, 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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| Keywords | HBV / RNA degradation / MafF / IL-1b / HBV-pgRNA |
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| Outline of Annual Research Achievements |
We previously showed that the inflammatory cytokine IL-1b induced HBV-RNA degradation through the induction of Ski2 (an important adaptor of RNA-exosome, and RNA degradation). Interestingly Marwa showed that IL-1b suppressed HBV-pgRNA levels, and that this suppression was regulated by MafF. We found MafF binding site on HBV-core promoter where MafF acted as a transcriptional repressor. However, mutations in this MafF binding site, blocking MafF/HBV-core promoter interaction, partially (1/3) rescued HBV-pgRNA levels. These data suggested another mechanism by which MafF suppress HBV-pgRNA. Northern blot analysis showed that MafF induced HBV-pgRNA degradation. Marwa is recently analyzing the mechanism of RNA decay affected by MafF.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Marwa identified two different mechanisms by which MafF suppress HBV replication. She showd that MafF directly interact and suppress transcription from HBV-core promoter. She also showed that MafF suppress HBV-pgRNA levels through the induction of its degradation. From now on, she will focus on analyzing the mechanism by which MafF induce this degradation.
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| Strategy for Future Research Activity |
From now on, she will focus on analyzing the mechanism by which MafF induce this degradation. Loss of function of key factor s (EXOSC3, HBS1L, Ski2, XRN1,...) will be performed, and its effect on MafF regulation of HBV-pgRNA decay will be analyzed.The effect of MafF on the expression of the identified factors will be quantified. The mechanism by which MafF affect the expression of these genes, and its regulation by anti-viral cytokines will be further investigated. Data will be drafted into a paper and submitted.
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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,
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)
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
