The Analysis of the immune evasion strategy by hepatitis C virus

• Project/Area Number: 25860522
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NITTA Sayuri 東京医科歯科大学, 医歯(薬)学総合研究科, 特任助教 (20527056)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: C型肝炎 / 自然免疫応答 / ウイルス / 免疫学 / 細胞・組織 / インターフェロン

Outline of Final Research Achievements

Nearly 70% of HCV infected patients develop chronic hepatitis, which leads to liver cirrhosis and hepatocellular carcinoma. Some viral proteins of HCV have been reported to block the host antiviral immune response that could cause persistent infection and chronic hepatitis. In this study, we have shown that non-structural protein 4B of HCV, especially N-terminus of NS4B, inhibit both of the IFNβ and the IFNλ by targeting STING which is signal molecule of IFN pathway. These results are important to understand the HCV evasion system from host antiviral response and may contribute to develop novel anti-HCV drugs.

Research Products

• [Journal Article] Hepatitis C virus NS4B protein targets STING and abrogates RIG-I-mediated type-I interferon-dependent innate immunity (2013)
  • Author(s): Nitta S, Sakamoto N, Nakagawa M, Kakinuma S, Mishima K, Kusano-kitazume A, Kiyohashi K, Murakawa M, Nishimura-Sakurai Y, Azuma S, Tasaka-Fujita M, asahina Y, Yoneyama M, Fujita T, Watanabe M
  • Journal Title: Hepatology Volume: 57 Issue: 1 Pages: 46-58
  • DOI: 10.1002/hep.26017
  • Peer Reviewed
• [Journal Article] Wnt5a Signaling Mediates Biliary Differentiation of Fetal Hepatic Stem/Progenitor Cells (2013)
  • Author(s): Kakinuma S, Kiyohashi K, Kamiya A, Sakamoto N, Nitta S, Yamanaka H, YoshinoK, Fujiki J, Murakawa M, Kusano-Kitazume A, Shimizu H, Okamoto R, Azuma S, Nakagawa M, Asahina Y, Tanimizu N, Kikuchi A, Nakauchi H, and *WatanabeM
  • Journal Title: Hepatology Volume: (in press) Issue: 6 Pages: 2502-2513
  • DOI: 10.1002/hep.26293
  • Peer Reviewed
• [Presentation] HCV-NS4BのIFN-λ抑制作用に関する解析 (2014)
  • Author(s): 新田沙由梨、朝比奈靖浩、坂本直哉、後藤文男、谷口未樹、河合富貴子、大谷賢志、村川美也子、中川美奈、柿沼晴、渡辺守
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ（東京）
  • Year and Date: 2014-05-30
• [Presentation] HCV-NS4BはIFN-β発現誘導だけでなくIFN-λ発現誘導も抑制する
  • Author(s): 新田 沙由梨
  • Organizer: JDDW2013 第17回 日本肝臓学会大会
  • Place of Presentation: 東京
• [Presentation] HCV-NS4BによるSTINGを標的とした自然免疫応答回避メカニズムの解析
  • Author(s): 新田 沙由梨
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] HCV-NS4B protein blocks both type I and type III IFN production
  • Author(s): Nitta Sayuri
  • Organizer: 20th International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Melborne, Australia
• [Book] Liver Forum in Kyoto 第16回学術集会記録集 (2014)
  • Author(s): 新田沙由梨
  • Total Pages: 76
  • Publisher: メディカルトリビューン