Characterization of adapted HCV that can replicate efficiently in non-hepatic cells

• Project/Area Number: 15K19110
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: Ono Chikako 大阪大学, 微生物病研究所, 特任研究員(常勤) (30626437)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: C型肝炎ウイルス / 感染症 / 肝外病変 / マイクロRNA

Outline of Final Research Achievements

A liver-specific microRNA, miR-122, is one of the key determinants of hepatotropism of hepatitis C virus (HCV). We established mutant viruses with adaptive mutations in the 5’UTR of HCV RNA adjacent to miR-122 binding sites, which exhibits efficient RNA replication in miR-122-deficient condition. Furthermore, same adaptive mutation was detected from HCV-RNA replicating in non-hepatic cells of chronic HCV patients. These results suggest that HCV mutants capable of replicating in the absence of miR-122 may participate in the induction of extrahepatic manifestations in chronic hepatitis C patients.

Research Products

• [Journal Article] Characterization of miR-122-independent propagation of HCV (2017)
  • Author(s): C. Ono, T. Fukuhara, D. Motooka, S. Nakamura, D. Okuzaki, S. Yamamoto, T. Tamura, H. Mori, A. Sato, K. Uemura, Y. Fauzyah, T. Kurihara, T. Suda, A. Nishio, Su Su Hmwe, T. Okamoto, T. Tatsumi, T. Takehara, K. Chayama, T. Wakita, K. Koike, Y. Matsuura
  • Journal Title: PLoS Pathogens Volume: - Issue: 5 Pages: e1006374-e1006374
  • DOI: 10.1371/journal.ppat.1006374
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Human cathelicidin compensates for the role of apolipoproteins in the infectious particle formation of HCV. (2016)
  • Author(s): Puig-Basagoiti F., Fukuhara T., Tamura T., Ono C., Uemura K., Kawachi Y., Yamamoto S., Mori H., Kurihara T., Okamoto T., Aizaki H., Matsuura Y.
  • Journal Title: Journal of Virology Volume: 90 Issue: 19 Pages: 1-14
  • DOI: 10.1128/jvi.00471-16
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of Lipoproteins and Apolipoproteins in Particle Formation of Hepatitis C Virus (2015)
  • Author(s): Fukuhara T, Ono C, Puig-Basagoiti F, Matsuura Y
  • Journal Title: Trends in Microbiology Volume: 23 Issue: 10 Pages: 618-629
  • DOI: 10.1016/j.tim.2015.07.007
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] G28A mutation facilitates an efficient propagation of HCV in miR-122-independent manner (2016)
  • Author(s): 小野慎子，福原崇介，元岡大祐，中村昇太，山本聡美，森寛行，上村健太朗，岡本徹，Su Su Hmwe，茶山一彰，脇田隆字，小池和彦，松浦善治
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-10-24
  • Int'l Joint Research
• [Presentation] G28A mutation is necessary for an efficient propagation of HCV in miR-122 deficient condition (2016)
  • Author(s): 小野慎子，福原崇介，元岡大祐，中村昇太，山本聡美，森寛行，上村健太朗，岡本徹，Su Su Hmwe，茶山一彰，脇田隆字，小池和彦，松浦善治
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-10-12
  • Int'l Joint Research
• [Presentation] CHARACTERIZATION OF MIR-122-INDEPENDENT PROPAGATION OF HCV (2016)
  • Author(s): 小野慎子，福原崇介，山本聡美，森寛行，上村健太朗，河内悠華子，岡本徹，Su Su Hmwe，脇田隆字，小池和彦，松浦善治
  • Organizer: American Society for Virology 2016 Meeting
  • Place of Presentation: Virginia Tech
  • Year and Date: 2016-06-19
  • Int'l Joint Research
• [Presentation] Characterization of miR-122-independent propagation of HCV (2015)
  • Author(s): Chikako Ono, Takasuke Fukuhara, Satomi Yamamoto, Hiroyuki Mori, Toru Okamoto, Su Su Hmwe, Takaji Wakita, Kazuhiko Koike and Yoshiharu Matsuura
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2015-11-22
• [Presentation] Characterization of miR-122-independent propagation of HCV (2015)
  • Author(s): Chikako Ono, Takasuke Fukuhara, Satomi Yamamoto, Hiroyuki Mori, Toru Okamoto, Su Su Hmwe, Takaji Wakita, Kazuhiko Koike and Yoshiharu Matsuura
  • Organizer: 22nd International symposium on Hepatitis C and related viruses
  • Place of Presentation: フランス、ストラスブール
  • Year and Date: 2015-10-09
  • Int'l Joint Research