Mechanistic analysis of post-traslational modification of viral RNA and its anti-viral application

2020 Fiscal Year Annual Research Report

• Project/Area Number: 18F18098
• Research Institution: National Institute of Infectious Diseases
• 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)
• 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
• Project Period (FY): 2018-10-12 – 2021-03-31
• Keywords: HBV / pgRNA / MafF

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).

Research Progress Status

令和2年度が最終年度であるため、記入しない。

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。

Research Products

• [Journal Article] MafF is an antiviral host factor that suppresses transcription from Hepatitis B Virus core promoter (2021)
  • Author(s): Ibrahim Marwa K.、Abdelhafez Tawfeek H.、Takeuchi Junko S.、Wakae Kosho、Sugiyama Masaya、Tsuge Masataka、Ito Masahiko、Watashi Koichi、El Kassas Mohamed、Kato Takanobu、Murayama Asako、Suzuki Tetsuro、Chayama Kazuaki、Shimotohno Kunitada、Muramatsu Masamichi、Aly Hussein H.、Wakita Takaji
  • Journal Title: Journal of Virology Volume: 「－」 Pages: 「－」
  • DOI: 10.1128/jvi.00767-21
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Current situation of viral hepatitis in Egypt (2021)
  • Author(s): Elbahrawy Ashraf、Ibrahim Marwa K.、Eliwa Ahmed、Alboraie Mohamed、Madian Ali、Aly Hussein Hassan
  • Journal Title: Microbiology and Immunology Volume: 「－」 Pages: 「－」
  • DOI: 10.1111/1348-0421.12916
  • Peer Reviewed / Int'l Joint Research
• [Presentation] MafF is a novel host restriction factor for HBV which suppresses transcription from HBV-core promoter (2020)
  • 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)
  • Int'l Joint Research