Viral regulation of host RNA degradation and its implication on hepatocarcinogenesis.

2020 Fiscal Year Research-status Report

• Project/Area Number: 19K07586
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: SKIV2L / HBx / HBV / Viral Life Cycle / RNA Exosome / RNA degradation

Outline of Annual Research Achievements

We found that hepatitis B virus can control the expression of SKIV2L through the function of HBx protein. In 2020 we aimed to investigate the host factors that are targeted by SKIV2L/RNA exosome system and affect viral pathogenesis. RNA-seq analysis was performed, and we identified that the expression of several interferon stimulated genes (ISGs) and cancer suppressor genes has been increased after silencing of SKIV2L. These data were confirmed by real time PCR. We also analyzed the role of SKIV2L on another Hepatitis virus (HDV). Interestingly, we found that suppressing SKIV2L expression significantly suppressed HDV RNA titer. Confirming that SKIV2L/RNA exosome system is involved in the regulation of several viral infection.

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

Because of SARS-CoV-2 pandemic, and the spread of the virus in Tokyo. Telework was implemented, since our research require experiments which can only be produced in the laboratory the progress of the project has been slightly delayed.

Strategy for Future Research Activity

In 2021, we aim to understand the role of the ISGs, and cancer suppressor genes identified by the RNA-seq analysis on viral life cycle. To do that HBV, or HDV infection will be conducted in cells lacking the expression of these genes; rescue experiments will be performed by gain of function, and the effect of these genes on viral life cycle, and/or acquiring carcinogenic phenotype will be monitored. These data will be followed by mechanistic analysis using protein/protein interaction experiments to identify interacting molecules, confocal microscopy will be used for the subcellular localization and co-localization, .... until the entire mechanism is revealed.

Research Products

• [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: 65 Pages: 352～372
  • DOI: 10.1111/1348-0421.12916
  • Peer Reviewed / Int'l Joint Research
• [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] N‐Terminal PreS1 Sequence Regulates Efficient Infection of Cell‐Culture?Generated Hepatitis B Virus (2020)
  • Author(s): Murayama A、Yamada N、Osaki Y、Shiina M、Aly H H、Iwamoto M、Tsukuda S、Watashi K、Matsuda M、Suzuki R、Tanaka T、Moriishi K、Suzuki T、Nishitsuji H、Sugiyama M、Mizokami M、Shimotohno K、Wakita T、Muramatsu M、Liang T. J、Kato T
  • Journal Title: Hepatology Volume: 73 Pages: 520～532
  • DOI: 10.1002/hep.31308
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anti‐viral effects of interferon‐λ3 on hepatitis B virus infection in cell culture (2020)
  • Author(s): Yamada Norie、Murayama Asako、Shiina Masaaki、Aly Hussein Hassan、Iwamoto Masashi、Tsukuda Senko、Watashi Koichi、Tanaka Tomohisa、Moriishi Kohji、Nishitsuji Hironori、Sugiyama Masaya、Mizokami Masashi、Shimotohno Kunitada、Muramatsu Masamichi、Murata Kazumoto、Kato Takanobu
  • Journal Title: Hepatology Research Volume: 50 Pages: 283～291
  • DOI: 10.1111/hepr.13449
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] MCPIP1 reduces HBV-RNA by targeting its epsilon structure (2020)
  • Author(s): Li Yingfang、Que Lusheng、Fukano Kento、Koura Miki、Kitamura Kouichi、Zheng Xin、Kato Takanobu、Aly Hussein Hassan、Watashi Koichi、Tsukuda Senko、Aizaki Hideki、Watanabe Noriyuki、Sato Yuko、Suzuki Tadaki、Suzuki Hiroshi I.、Hosomichi Kazuyoshi、Kurachi Makoto、Wakae Kousho、Muramatsu Masamichi
  • Journal Title: Scientific Reports Volume: 10 Pages: 「－」
  • DOI: 10.1038/s41598-020-77166-z
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The IL-1 β induced (MafF) is an important regulator of HBV core promoter activity (2020)
  • Author(s): 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.
  • Int'l Joint Research