Cross-talk regulation of viral replication and fatty acid synthesis by miRNAs

• Project/Area Number: 24590565
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: MUNAKATA Tsubasa 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (50420237)
• Research Collaborator: KOHARA Michinori 東京都医学総合研究所, ゲノム医科学研究分野, プロジェクトリーダー (10250218) ; SAITO Makoto 東京都医学総合研究所, ゲノム医科学研究分野, 主任研究員 (20433021)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: マイクロＲＮＡ / 脂肪酸合成酵素 / Ｃ型肝炎ウイルス / C型肝炎ウイルス / ウイルス複製 / 脂肪酸合成 / C型肝炎 / ウイルス / マイクロRNA / miRNA

Outline of Final Research Achievements

It is reported that miR-199a-3p represses HCV replication by targeting 5’ untranslated region (UTR) of HCV genomic RNA. On the other hand, induction of the lipogenesis pathway upon HCV infection is known to play an important role in regulating HCV propagation and pathogenesis. We have reported that fatty acid synthase (FASN), an enzyme essential for de novo synthesis of a fatty acid, was induced by HCV infection and replication, and that FASN was needed for the efficient replication of HCV. Moreover, we have found that there is a functional interaction between HCV and FASN through miR-199a-5p and -3p. Interestingly, expression of miR-199a-5p and -3p is regulated by HCV replication. These data demonstrate that miR-199a-3p simultaneously represses HCV replication and FASN expression, and that there exists a crosstalk between HCV replication and host lipogenesis at the level of miRNA-mediated regulation.

Research Products

• [Journal Article] Novel pH-sensitive multifunctional envelope-type nanodevice for siRNA-based treatments for chronic HBV infection (2016)
  • Author(s): Yamamoto, N. Sato, Y. Munakata, T. Kakuni, M. Tateno, C. Sanada, T. Hirata, Y. Murakami, S. Tanaka, Y. Chayama, K. Hatakeyama, H. Hyodo, M. Harashima, H. Kohara, M.
  • Journal Title: Journal of hepatology Volume: 64 Issue: 3 Pages: 547-455
  • DOI: 10.1016/j.jhep.2015.10.014
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Persistent infection factor of HBV. (2015)
  • Author(s): *Munakata T, Yamamoto N, *Kohara M.
  • Journal Title: Nihon Rinsho Volume: 73 Pages: 357-360
• [Journal Article] Hepatitis C virus attenuates mitochondrial lipid β-oxidation by downregulating mitochondrial trifunctional-protein expression. (2015)
  • Author(s): Amako Y, Munakata T, Kohara M, Siddiqui A, Peers C, Harris M.
  • Journal Title: J Virol Volume: 89 Issue: 8 Pages: 4092-4101
  • DOI: 10.1128/jvi.01653-14
  • Peer Reviewed / Open Access
• [Journal Article] Suppression of hepatitis C virus replication by cyclin-dependent kinase inhibitors (2014)
  • Author(s): Tsubasa Munakata, Makoto Inada, Yuko Tokunaga, Takaji Wakita, Michinori Kohara, Akio Nomoto
  • Journal Title: Antiviral Research Volume: 108 Pages: 79-87
  • DOI: 10.1016/j.antiviral.2014.05.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Broad-spectrum detection of h5 subtype influenza a viruses with a new fluorescent immunochromatography system (2013)
  • Author(s): Sakurai A, Takayama K, Nomura N, Munakata T, Yamamoto N, Tamura T, Yamada J, Hashimoto M, Kuwahara K, Sakoda Y, Suda Y, Kobayashi Y, Sakaguchi N, Kida H, Kohara M, Shibasaki F
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e76753-e76753
  • DOI: 10.1371/journal.pone.0076753
  • Peer Reviewed
• [Journal Article] Histopathological evaluation of the diversity of cells susceptible to H5N1 virulent avian influenza virus (2013)
  • Author(s): Ogiwara H, Yasui F, Munekata K, Takagi-Kamiya A, Munakata T, Nomura N, Shibasaki F, Kuwahara K, Sakaguchi N, Sakoda Y, Kida H, Kohara M
  • Journal Title: Am. J. Pathol Volume: 184 Issue: 1 Pages: 171-183
  • DOI: 10.1016/j.ajpath.2013.10.004
  • Peer Reviewed / Open Access
• [Journal Article] A serine palmitoyltransferase inhibitor blocks hepatitis C virus replication in human hepatocytes. (2013)
  • Author(s): Katsume A, Tokunaga Y, Hirata Y, Munakata T, Saito M, Hayashi H, Okamoto K, Ohmori Y, Kusanagi I, Fujiwara S, Tsukuda T, Aoki Y, Klumpp K, Tsukivama-Kohara K, El-Gohary A, Sudoh M, Kohara M.
  • Journal Title: Gastroenterology Volume: 145(4) Issue: 4 Pages: 865-79
  • DOI: 10.1053/j.gastro.2013.06.012
  • Peer Reviewed
• [Presentation] Novel pH-sensitive multifunctional envelope-type nanodevice for siRNA-based treatments for chronic HBV infection. (2015)
  • Author(s): Naoki Yamamoto, Yusuke Sato, Tsubasa Munakata, Takahiro Sanada, Masakazu Kakuni, Chise Tateno, Hideyoshi Harashima and *Michinori Kohara
  • Organizer: 第38回日本分子生物学会学術集会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] siRNA-based therapies to chronic HBV infection using a novel pH-sensitive multifunctional envelope-type nanodevice. (2015)
  • Author(s): *Naoki Yamamoto, Yusuke Sato, Tsubasa Munakata, Takahiro Sanada, Masakazu Kakuni, Chise Tateno, Shuko Murakami, Yasuhito Tanaka, Kazuaki Chayama, Hideyoshi Harashima, Michinori Kohara
  • Organizer: 2015 International Meeting on Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: バート・ナウハイム、ドイツ
  • Year and Date: 2015-10-04
  • Int'l Joint Research
• [Presentation] C型肝炎ウイルス感染時にTLR3はIFN非依存的に発現して抗ウイルス作用を示す. (2014)
  • Author(s): 棟方 翼、徳永 優子、真田 崇弘、脇田 隆字、野本 明男、小原 道法.
  • Organizer: 第62回日本ウイルス学会学術集会.
  • Place of Presentation: パシフィコ横浜会議センター、横浜.
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Suppression of Hepatitis C Virus Replication by Cyclin-dependent Kinase Inhibitors. (2014)
  • Author(s): Tsubasa Munakata, Makoto Inada, Yuko Tokunaga, Takaji Wakita, Michinori Kohara, and Akio Nomoto.
  • Organizer: 21st International Symposium on Hepatitis C and Related Viruses.
  • Place of Presentation: The Fairmont Banff Springs, Banff, Canada.
  • Year and Date: 2014-09-07 – 2014-09-11
• [Presentation] C型肝炎ウイルス感染時にToll-like receptor 3の発現はRb/E2F経路で制御される (2012)
  • Author(s): 棟方 翼、脇田 隆字、野本 明男、小原 道法
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪国際会議場、大阪
• [Presentation] 新世代抗体医薬としての特殊環状ペプチドによるインフルエンザウイルス増殖阻害効果 (2012)
  • Author(s): 齊藤 誠、飛田 良美、棟方 翼、伊東 利紗、菅 裕明、佐々木 亨、窪田 規一、安井 文彦、小澤 真、小原 恭子、小原 道法
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪国際会議場、大阪
• [Presentation] HEPATIC TOLL-LIKE RECEPTOR 3 INDUCED BY E2F1 CONTROLS HEPATITIS C VIRAL REPLICATION. (2012)
  • Author(s): Tsubasa Munakata, Akio Nomoto, and Michinori Kohara
  • Organizer: The 19th International Symposium on Hepatitis C Virus and Related Viruses.
  • Place of Presentation: Venice, Italy
• [Presentation] MicroRNAs regulating lipogenesis attenuate hepatitis C viral infection by two distinct pathways
  • Author(s): Tsubasa Munakata, Takeshi Haraguchi, Hideo Iba, and Michinori Kohara
  • Organizer: キーストーン・シンポジウム：ウイルス感染に対する自然免疫
  • Place of Presentation: キーストーン・カンファレンス・センター、コロラド、アメリカ
• [Presentation] マイクロRNAによるC型肝炎ウイルス複製制御と宿主脂肪酸合成経路のクロストーク
  • Author(s): 棟方 翼、原口 健、伊庭 英夫、小原 道法
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸国際会議場、神戸、日本
• [Presentation] A crosstalk between HCV replication and host lipogenesis is mediated by miRNAs
  • Author(s): Tsubasa Munakata, Takeshi Haraguchi, Hideo Iba, and Michinori Kohara
  • Organizer: 第20回国際Ｃ型肝炎ウイルス及び関連ウイルスシンポジウム
  • Place of Presentation: メルボルン・コンベンション・エキシビション・センター、メルボルン、オーストラリア
• [Presentation] Hepatic Fatty acid synthase and Toll-like receptor 3 induced by E2F1 control hepatitis C viral replication.
  • Author(s): Tsubasa Munakata
  • Organizer: 3rd Igakuken International Symposium on Control of Influenza and Hepatitis.
  • Place of Presentation: Tokyo, Japan
  • Invited