Viral regulation of host RNA degradation and its implication on hepatocarcinogenesis
Project/Area Number |
19K07586
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49060:Virology-related
|
Research Institution | National Institute of Infectious Diseases |
Principal Investigator |
Aly Hussein H 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
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
Keywords | SKIV2L / HBV / RNA degradation / HBx / Viral Life Cycle / RNA Exosome / Ski2 / Viral life cycle / Hepatitis B Virus / Virology |
Outline of Research at the Start |
By controlling mRNA stability, the virus can manipulate several cellular responses, and cellular environment to favor its persistence. This manipulation may lead to continuous alteration of cellular environment and cancer development. We found that hepatitis B virus can control the expression of Ski2 leading to the degradation of HBx mRNA at the Ski2/RNA exosome system. Using in-vitro and in-vivo mouse model systems, we aim to analyze the functional significance of regulating this RNA degradation mechanism on HBV persistence, and its possible contribution to HBV-induced hepatocarcinogenesis.
|
Outline of Final Research Achievements |
We found that HBx protein significantly induced the expression of the RNA exosome co-factor (SKIV2L) suggesting that it may regulate the stability of other host /viral mRNA. Silencing of SKIV2L significantly enhanced the expression of OAS2. Hepatitis Delta Virus (HDV) is a satellite virus that depends on HBV. We found that SKIV2L significantly induced HDV replication. OAS2 played important role in this regulation. We hypothesized that HBx may increase cellular permissiveness to HDV infection by increasing SKIV2L levels and in turn suppressing OAS2 expression. We did not find any significant effect of HBx expression on OAS2 levels. We observed similar results by transfecting WT or a mutant HBV lacking the expression of HBx. From these results we concluded that there are no significant effect of SKIV2L on the HBx-mediated changes in cellular transcriptome. We also found that SKIV2L plays an important role in supporting HDV infection by suppressing host ISGs especially OAS2.
|
Academic Significance and Societal Importance of the Research Achievements |
We found that the RNA exosome co-factor (SKIV2L) regulate Hepatitis Delta Virus (HDV) replication by the suppression of interferon stimulated gene (OAS2) expression.
|
Report
(4 results)
Research Products
(16 results)
-
-
[Journal Article] Interferon-gamma induced APOBEC3B contributes to Merkel cell polyomavirus genome mutagenesis in Merkel cell carcinoma2021
Author(s)
Que L, Li Y, Dainichi T, Kukimoto I, Nishiyama T, Nakano Y, Shima K, Suzuki T, Sato Y, Horike S, Aizaki H, Watashi K, Kato T, Aly HH, Watanabe N, Kabashima K, Wakae K, Muramatsu M.
-
Journal Title
J Invest Dermatol
Volume: S0022-202X(21)
Issue: 7
Pages: 02636-1
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
[Journal Article] MCPIP1 reduces HBV-RNA by targeting its epsilon structure2020
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
Issue: 1
Pages: 20763-20763
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Presentation] Kinesin KIF4 is a key regulator for surface localization of NTCP, and HBV/HDV infection2021
Author(s)
Sameh A. Gad, Masaya Sugiyama, Masataka Tsuge, Kosho Wakae, Kento Fukano, Noriyuki Watanabe, Takanobu Kato, Asako Murayama, Yingfang Li, Ikuo Shoji, Kunitada Shimotohno, Kazuaki Chayama, Masamichi Muramatsu, Takaji Wakita, Tomoyoshi Nozaki, Hussein H. Aly
Organizer
2021 International Meeting, Biology of the Hepatitis B and D Viruses
Related Report
Int'l Joint Research
-
[Presentation] Kinesin KIF4 is a possible therapeutic host target and key regulator for surface localization of NTCP, and HBV/HDV infection2021
Author(s)
Sameh A. Gad, Masaya Sugiyama, Masataka Tsuge, Kosho Wakae, Kento Fukano, Noriyuki Watanabe, Takanobu Kato, Asako Murayama, Yingfang Li, Ikuo Shoji, Kunitada Shimotohno, Kazuaki Chayama, Masamichi Muramatsu, Takaji Wakita, Tomoyoshi Nozaki, Hussein H. Aly
Organizer
The 68th Annual Meeting of the Japanese Society for Virology
Related Report
-
-
[Presentation] The IL-1 β induced (MafF) is an important regulator of HBV core promoter activity2020
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.
Related Report
Int'l Joint Research
-
[Presentation] MafF is a key player of IL-1β-induced suppression of transcription from HBV-core promoter, and the resulting suppression of viral replication2019
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
Related Report
Int'l Joint Research
-
[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.
Related Report
-
[Presentation] MAFF IS AN IMPORTANT REGULATOR OF HBV CORE PROMOTER ACTIVITY, AND HBV REPLICATION2019
Author(s)
Marwa K. Ibrahim, Sameh A. Gad, Koichi Watashi, Takanobu Kato, Asako Murayama, Kunitada Shimotohno, Takaji Wakita, Masamichi Muramatsu, Hussein H. Aly
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