To analyze the mechanisms of HCV drug resistance by using chimeric HCV cell culture system
| Project/Area Number |
25860513
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Hokkaido University |
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Principal Investigator |
SUDA Goki 北海道大学, 医学(系)研究科(研究院), 特任助教 (20447460)
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| Co-Investigator(Renkei-kenkyūsha) |
SAKAMOTO Naoya 北海道大学, 大学院医学研究科, 教授 (10334418)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥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)
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| Keywords | ＨＣＶ / ＩＦＮ / 薬剤耐性ウイルス / HCV |
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| Outline of Final Research Achievements |
The mechanism of HCV resistance to IFN has not been wellunderstood. We conducted homologous recombination between HCV-2b and JFH1 and ensured that the chimeric virus could be long-cultured. Then we long-cultured HCV-2b/JFH1 chimeric virus (C3) with or without IFN and compared virus kinetics between the two groups, and tried to extract IFN resistant clone. Supernatant HCV of C3 decreased immediately. However, 6 weeks after IFN treatment, replication of one C3 clone increased . Comparison of amino acid sequences revealed two sequence differences in structure region. Next we constructed these two sequence differences substituted C3 clone (IFNrC3) and compared IFN sensitivity between IFNrC3 and C3 by transfection into cells and subsequently IFN treatment. The newly constructed IFNrC3 showed resistance to IFN.
Additionally, we investigated prevalence of resistant HCV against DAA in japan by using NGS. The existence of resistant virus did not affect treatment outcome in TPV based therapy.
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] EGFR inhibitors eliminate cancer stem-like cells in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition2015
Author(s)
１．Fumiyuki Sato, Yoshimasa Kubota, Mitsuteru Natsuizaka, Osamu Maehara, Yutaka Hatanaka, Katsuji Marukawa, Katsumi Terashita, Goki Suda, Shunsuke Ohnishi, Yuichi Shimizu, Yoshito Komatsu, Shinya Ohashi, Shingo Kagawa, Hideaki Kinugasa, Kelly Whelan, Anil Rustgi, Hiroshi Nakagawa, and Naoya Sakamoto
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Journal Title
Cancer Biology & Therapy
Volume: Epub ahead of print
Related Report
Peer Reviewed
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[Journal Article] Human amnion-derived mesenchymeal stem cell transplantation ameliorates dextran sulfate sodium-induced severe colitis in rats.2015
Author(s)
２．Onishi R, Ohnishi S, Higashi R, Watari M, Yamahara K, Okubo N, Nakagawa K, Katsurada T, Suda G, Natsuizaka M, Takeda H, Sakamoto N
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Journal Title
Cell Transplantation
Volume: Epub ahead of print
NAID
Related Report
Peer Reviewed
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[Journal Article] Intratumoral artery on contrast-enhanced computed tomography imaging: differentiating intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma2015
Author(s)
３．Tsunematsu S1, Chuma M, Kamiyama T, Miyamoto N, Yabusaki S, Hatanaka K, Mitsuhashi T, Kamachi H, Yokoo H, Kakisaka T, Tsuruga Y, Orimo T, Wakayama K, Ito J, Sato F, Terashita K, Nakai M, Tsukuda Y, Sho T, Suda G, Morikawa K, Natsuizaka M, Nakanishi M, Ogawa K, Taketomi A, Matsuno Y, Sakamoto N
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Journal Title
Abdom Imaging.
Volume: Epub ahead of print
Related Report
Peer Reviewed
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[Journal Article] Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions.2015
Author(s)
Suda G, Yamamoto Y, Nagasaka A, Furuya K, Kudo M, Chuganji Y, Tsukuda Y, Tsunematsu S, Sato F, Terasita K, Nakai M, Horimoto H, Sho T, Natsuizaka M, Ogawa K, Ohnishi S, Chuma M, Fujita Y, Abe R, Taniguchi M, Nakagawa M, Asahina Y, Sakamoto N
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Journal Title
Hepatol Res
Volume: 印刷中
Issue: 8
Pages: 837-45
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Heat shock factor 1 accelerates hepatocellular carcinoma development by activating nuclear factor κB/mitogen-activated protein kinase.2014
Author(s)
Chuma M, Sakamoto N, Nakai A, Hige S, Nakanishi M, Natsuizaka M, Suda G, Sho T, Hatakaka K, Matsuno Y, Yokoo H, Kamiyama T, Taketomi A, Fujii G, Tashiro K, Hikiba Y, Fujimoto M, Asaka M, Maeda S
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Journal Title
Carcinogenesis
Volume: Epub ahead of print
Issue: 2
Pages: 272-281
DOI
Related Report
Peer Reviewed
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[Journal Article] Hepatosplenic Gamma-delta T-cell Lymphoma Associated with Epstein-Barr Virus2014
Author(s)
６．Seiji Tsunematsu, Mitsuteru Natsuizaka, Hiromi Fujita, Noriyuki Otsuka, Katsumi Terashita, Fumiyuki Sato, Tomoe Kobayashi, Masato Nakai, Yoko Tsukuda, Hiromasa Horimoto, Takuya Sho, Goki Suda, Mitsuru Nakanishi, Satoshi Hashino, Makoto Chuma, Naoya Sakamoto
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Journal Title
Intern Med
Volume: 53(18)
Pages: 2079-2082
NAID
Related Report
Peer Reviewed
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[Presentation] Serum granulysin level is correlated with severity of telaprevir induced dermatological adverse reactions and could be a useful predictor2014
Author(s)
Goki Suda , Yoshiya Yamamoto, Astusi Nagasaka, Ken Furuya, Yoko Tsukuda, Seiji Tsunematsu, Fumiyuki Satou, Katsumi Terasita, Keita Horimoto, Takuya Sh Masato Nakai, Mitsuteru Natsuizka, Makoto Chuma , Naoya Sakamoto
Organizer
Asian Pacific Association for The Study of the Liver
Place of Presentation
Brisbane Convention & Exhibition Centre（Brisbene）, Australia
Related Report
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