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Analysis of mechanisms for suppressing interferon responsiveness by chronic hepatitis B virus infection

Research Project

Project/Area Number 15K09002
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

TSUGE MASATAKA  広島大学, 自然科学研究支援開発センター, 助教 (50448263)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsB型肝炎ウイルス / 遺伝子発現 / インターフェロン / 治療抵抗性
Outline of Final Research Achievements

It is considered that many gene expressions are regulated by hepatitis B virus (HBV) infection and this regulation of gene expressions are different among infected HBV genotypes. Howevere, it has not been clarified the differences of regulation in gene expresions among HBV genotypes. In the present study, I analyzed gene expression profiles using human hepatocytes with or without HBV infection and then I also analyzed the association between HBV related proteins and the regulated genes via HBV infection. By gene expression analysis, it was identified that regulation levels in several gene expressions were different between HBV genotype A and C infection. And further analyses were indicated that transcription of one gene was regulated by HBx and HBs protein and the upregulation of this gene suppressed interferon responsiveness in human hepatocytes.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (38 results)

All 2018 2017 2016 2015 2014

All Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 15 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Combinational use of2018

    • Author(s)
      Matsumoto A, Nishiguchi S, Enomoto H, Kang JH, Tanaka Y, Shinkai N, Kurosaki M, Enomoto M, Kanda T, Yokosuka O, Yatsuhashi H, Nagaoka S, Okuse C, Kagawa T, Mine T, Takaguchi K, Saito S, Hino K, Ikeda F, Sakisaka S, Morihara D, Miyase S, Tsuge M, Chayama K, Hiramatsu N, Suzuki Y, Murata K, Tanaka E
    • Journal Title

      J Gastroenterol

      Volume: 53 Issue: 2 Pages: 247-257

    • DOI

      10.1007/s00535-017-1360-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a novel site-specific pegylated interferon beta for antiviral therapy for chronic hepatitis B.2017

    • Author(s)
      Tsuge M, Uchida T, Hiraga N, Kan H, Makokha GN, Abe-Chayama H, Miki D, Imamura M, Ochi H, Hayes CN, Shimozono R, Iwamura T, Narumi H, Suzuki T, Kainoh M, Taniguchi T, Chayama K.
    • Journal Title

      Antimicrob Agents Chemother.

      Volume: 印刷中 Issue: 6 Pages: 61-61

    • DOI

      10.1128/aac.00183-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Persistent loss of HBV markers in serum without cellular immunity by combination of PEG-IFN plus ETV therapy in humanized mice2017

    • Author(s)
      Uchida T, Imamura M, Hayes CN, Hiraga N, Kan H, Tsuge M, Abe-Chayama H, Zhang Y, Makokha GN, Aikata H, Miki D, Ochi H, Ishida Y, Tateno C, Chayama K
    • Journal Title

      Antimicrob Agents Chemother

      Volume: 61 Issue: 9

    • DOI

      10.1128/aac.00725-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of humanized cDNA-uPA/SCID mice for the study of hepatitis B virus and hepatitis C virus virology.2017

    • Author(s)
      Uchida T, Imamura M, Kan H, Hiraga N, Hayes CN, Tsuge M, Abe-Chayama H, Aikata H, Makokha GN, Miki D, Ochi H, Ishida Y, Tateno C, Chayama K.
    • Journal Title

      J Gen Virol.

      Volume: 印刷中 Issue: 5 Pages: 1040-1047

    • DOI

      10.1099/jgv.0.000726

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The relationship between HBcrAg and HBV reinfection in HBV related post-liver transplantation patients.2017

    • Author(s)
      Urabe A, Imamura M, Tsuge M, Kan H, Fujino H, Fukuhara T, Masaki K, Kobayashi T, Ono A, Nakahara T, Kawaoka T, Hiramatsu A, Kawakami Y, Aikata H, Hayes CN, Maki N, Ohdan H, Chayama K.
    • Journal Title

      J Gastroenterol.

      Volume: 52 Issue: 3 Pages: 366-375

    • DOI

      10.1007/s00535-016-1240-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The prognosis of hepatitis B inactive carriers in Japan: a multicenter prospective study.2017

    • Author(s)
      Taida T., Arai M., Kanda T., Hige S., Ueno Y., Imazeki F., Izumi N., Tanaka E., Shinkai N., Yoshioka K., Nakamoto Y., Nishiguchi S., Tsuge M., Abe M., Sata M., Yatsuhashi H., Ido A., Kita K., Azemoto R., Kitsukawa Y., Goto N. and Yokosuka O.
    • Journal Title

      Journal of Gastroenterology

      Volume: 52 Issue: 1 Pages: 113-122

    • DOI

      10.1007/s00535-016-1229-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elimination of HCV via a non-ISG-mediated mechanism by vaniprevir andBMS-788329 combination therapy in human hepatocyte chimeric mice.2016

    • Author(s)
      Uchida T, Hiraga N, Imamura M, Yoshimi S, Kan H, Miyaki E, Tsuge M, Abe H, Hayes CN, Aikata H, Ishida Y, Tateno C, Ellis JD, Chayama K.
    • Journal Title

      Virus Res.

      Volume: 213 Issue: 1 Pages: 62-68

    • DOI

      10.1016/j.jinf.2015.09.038

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection.2016

    • Author(s)
      Tsuge M, Hiraga N, Uchida T, Kan H, Miyaki E, Masaki K, Ono A, Nakahara T, Abe-Chayama H, Zhang Y, Naswa MG, Kawaoka T, Miki D, Imamura M, Kawakami Y, Aikata H, Ochi H, Hayes CN, Chayama K.
    • Journal Title

      Journal of Gastroenterology

      Volume: In press Issue: 11 Pages: 1073-1080

    • DOI

      10.1007/s00535-016-1189-x

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of chronic inflammatory demyelinating polyradiculoneuropathy after treatment with pegylated interferon α-2a in a patient with chronic hepatitis B virus infection2016

    • Author(s)
      Naito H., Takeda I., Segawa A., Tsuge M., Maruyama H. and Matsumoto M.
    • Journal Title

      Rinsho Shinkeigaku

      Volume: 56 Issue: 10 Pages: 672-677

    • DOI

      10.5692/clinicalneurol.cn-000888

    • NAID

      130005250055

    • ISSN
      0009-918X, 1882-0654
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] de novo B型肝炎のインパクト2016

    • Author(s)
      柘植雅貴、茶山一彰
    • Journal Title

      医学のあゆみ

      Volume: 258 Pages: 1144-1146

    • Related Report
      2016 Research-status Report
  • [Journal Article] Improvement of renal dysfunction in a patient with HCV-related liver cirrhosis by daclatasvir and asunaprevir combination therapy: A case report.2016

    • Author(s)
      Tsuge M, Hiramatsu A, Shinohara F, Nakano N, Nakamura Y, Hatooka M, Morio K, Morio R, Kan H, Fujino H, Uchida T, Kobayashi T, Fukuhara T, Masaki K, Nakahara T, Ono A, Nagaoki Y, Miki D, Kawaoka T, Hiraga N, Imamura M, Kawakami Y, Aikata H, Ochi H, Hayes CN, Chayama K.
    • Journal Title

      Hepatology Research

      Volume: 印刷中 Issue: 9 Pages: 944-948

    • DOI

      10.1111/hepr.12629

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection.2016

    • Author(s)
      Tsuge M, Hiraga N, Uchida T, Kan H, Miyaki E, Masaki K, Ono A, Nakahara T, Abe-Chayama H, Zhang Y, Naswa MG, Kawaoka T, Miki D, Imamura M, Kawakami Y, Aikata H, Ochi H, Hayes CN, Chayama K.
    • Journal Title

      Journal of Gastroenterology

      Volume: 印刷中

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Factors associated with the effect of interferon-alpha sequential therapy in order to discontinue nucleoside/nucleotide analog treatment in patients with chronic hepatitis B.2015

    • Author(s)
      Matsumoto A., Yatsuhashi H., Nagaoka S., Suzuki Y., Hosaka T., Tsuge M., Chayama K., Kanda T., Yokosuka O., Nishiguchi S., Saito M., Miyase S., Kang J.H., Shinkai N., Tanaka Y., Umemura T. and Tanaka E.
    • Journal Title

      Hepatology Research

      Volume: 45 Issue: 12 Pages: 1195-1202

    • DOI

      10.1111/hepr.12488

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differences in serum microRNA profiles in hepatitis B and C virus infection.2015

    • Author(s)
      Akamatsu S, Hayes CN, Tsuge M, Miki D, Akiyama R, Abe H, Ochi H, Hiraga N, Imamura M, Takahashi S, Aikata H, Kawaoka T, Kawakami Y, Ohishi W, Chayama K.
    • Journal Title

      J Infect.

      Volume: 70 Issue: 3 Pages: 273-287

    • DOI

      10.1016/j.jinf.2014.10.017

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human Cytotoxic T Lymphocyte-Mediated Acute Liver Failure and Rescue by Immunoglobulin in Human Hepatocyte Transplant TK-NOG Mice.2015

    • Author(s)
      Uchida T., Hiraga N., Imamura M., Tsuge M., Abe H., Hayes C.N., Aikata H., Ishida Y., Tateno C., Yoshizato K., Ohdan H., Murakami K. and Chayama K.
    • Journal Title

      Journal of Virology

      Volume: 89 Issue: 19 Pages: 10087-96

    • DOI

      10.1128/jvi.01126-15

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Human microRNA hsa-miR-1231 suppresses hepatitis B virus replication by targeting core mRNA.2014

    • Author(s)
      Kohno T, Tsuge M, Murakami E, Hiraga N, Abe H, Miki D, Imamura M, Ochi H, Hayes CN, Chayama K.
    • Journal Title

      J Viral Hepat.

      Volume: 21 Issue: 4 Pages: 369-375

    • DOI

      10.3851/imp2777

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 1.B型肝炎ウイルス(HBV)感染に伴う肝細胞内IL8発現亢進と細胞内インターフェロン反応性の検討2017

    • Author(s)
      柘植 雅貴、内田宅郎、茶山一彰
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 2.B型慢性肝疾患に対するエンテカビル治療と血清サイトカインの変化2017

    • Author(s)
      柘植 雅貴、栗原美緒、茶山一彰
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 3.核酸アナログ治療併用の有無によるインターフェロン治療効果の検討2017

    • Author(s)
      柘植雅貴、川上由育、茶山一彰
    • Organizer
      第21回日本肝臓学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 4.Hepatitis B virus up-regulates IL8 expression via endoplasmic reticulum stress and leads to suppress interferon responsiveness.2017

    • Author(s)
      Tsuge M, Hiraga N, Uchida T, Murakami E, Abe-Chayama H, Miki D, Imamura M, Kawakami Y, Aikata H, Ochi H, Hayes CN, Chayama K
    • Organizer
      AASLD(米国肝臓学会)2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 5.核酸アナログ治療例に対するペグインターフェロン治療とHBs低下に関する検討2017

    • Author(s)
      柘植雅貴、川上由育、内川慎介、児玉健一郎、西田祐乃、稲垣有希、盛生 慶、中原隆志、村上英介、河岡友和、平松 憲、今村道雄、相方 浩、川上広育、茶山一彰
    • Organizer
      第42回日本肝臓学会西部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] B型肝炎ウイルス感染に伴うヒト肝細胞内遺伝子の発現変化の解析2016

    • Author(s)
      柘植 雅貴、平賀伸彦、茶山一彰
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      千葉県幕張
    • Related Report
      2016 Research-status Report
  • [Presentation] 核酸アナログ投与B型慢性肝炎症例に対するHBIG投与の有効性2016

    • Author(s)
      柘植 雅貴、川上由育、茶山一彰
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      千葉県幕張
    • Related Report
      2016 Research-status Report
  • [Presentation] HBV genotypeに伴う核酸アナログ感受性に関する検討2016

    • Author(s)
      柘植 雅貴、村上英介、茶山 一彰
    • Organizer
      第102回日本消化器病学会総会
    • Place of Presentation
      東京都
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト肝細胞キメラマウスを用いたB型肝炎ウイルス遺伝子型による感染肝細胞内遺伝子発現変化の検討2016

    • Author(s)
      柘植雅貴、内田宅郎、菅宏美、阿部弘美、三木大樹、河岡友和、平賀伸彦、今村道雄、相方浩、越智秀典、茶山一彰
    • Organizer
      第12回広島肝臓プロジェクト研究センターシンポジウム
    • Place of Presentation
      広島県広島市
    • Related Report
      2016 Research-status Report
  • [Presentation] 核酸アナログ先行投与によるインターフェロン反応性の改善2016

    • Author(s)
      柘植雅貴、森奈美、長沖祐子、河岡友和、平松憲、今村道雄、川上由育、相方浩、辻恵二、川上広育、茶山一彰
    • Organizer
      DDW2016
    • Place of Presentation
      兵庫県神戸市
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト肝細胞キメラマウスを用いたB型肝炎ウイルス遺伝子型による感染肝細胞内遺伝子発現変化の検討2016

    • Author(s)
      柘植雅貴、平賀伸彦、内田宅郎、菅宏美、阿部弘美、三木大樹、河岡友和、今村道雄、相方浩、越智秀典、茶山一彰
    • Organizer
      臨床分子医学会2016
    • Place of Presentation
      東京都
    • Related Report
      2016 Research-status Report
  • [Presentation] Evaluation of antiviral effects of a novel site-specific pegylated interferon beta using humanized mouse model2016

    • Author(s)
      Masataka Tsuge, Takuro Uchida, Hiromi Kan, Hiromi Abe, Daiki Miki, Michio Imamura, Hidenori Ochi, C Nelson Hayes, Reiko Shimozono, Tomokatsu Iwamura, Hideki Narumi, Tomohiko Suzuki, Mie Kainoh, Tadatsugu Taniguchi, Kazuaki Chayama
    • Organizer
      AASLD2016
    • Place of Presentation
      米国、ボストン
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] HBV RNA量を用いた核酸アナログ中止後再燃予測2015

    • Author(s)
      柘植雅貴、川上広育、茶山一彰
    • Organizer
      第42回日本肝臓学会西部会(パネルディスカッション)
    • Place of Presentation
      名古屋
    • Year and Date
      2015-11-25
    • Related Report
      2015 Research-status Report
  • [Presentation] Difference of intracellular responses by HBV genotype A and C infection in humanized mouse model2015

    • Author(s)
      Masataka Tsuge, Nobuhiko Hiraga, Hiromi Abe, Daiki Miki, Michio Imamura, Hidenori Ochi, C Nelson Hayes, Kazuaki Chayama
    • Organizer
      AASLD2016(ポスター)
    • Place of Presentation
      米国(サンフランシスコ)
    • Year and Date
      2015-11-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] B型肝炎治療の現状2015

    • Author(s)
      柘植雅貴
    • Organizer
      JDDW 2015(ランチョンセミナー)
    • Place of Presentation
      東京
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] HBV genotype C感染例におけるHBs抗原消失に関する検討2015

    • Author(s)
      柘植雅貴、村上英介、茶山一彰
    • Organizer
      JDDW 2015(ワークショップ)
    • Place of Presentation
      東京
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] HBV genotypeと核酸アナログの抗ウイルス効果2015

    • Author(s)
      柘植 雅貴、村上英介、平賀 伸彦、阿部弘美、今村 道雄、秋田智之 、田中純子 、茶山 一彰
    • Organizer
      第11回広島肝臓プロジェクト研究センターシンポジウム(一般演題)
    • Place of Presentation
      広島
    • Year and Date
      2015-07-04
    • Related Report
      2015 Research-status Report
  • [Presentation] HBV感染に伴うmicroRNA発現変化と miRNAによるHBV複製制御2015

    • Author(s)
      柘植雅貴、平賀伸彦、村上英介、阿部弘美、三木大樹、河岡友和、平松 憲、今村道雄、川上由育、相方 浩、越智秀典、茶山一彰
    • Organizer
      第51回日本肝臓学会総会(一般演題)
    • Place of Presentation
      熊本
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 核酸アナログ中止例における HBVコア蛋白のアミノ酸変異に関する解析2015

    • Author(s)
      村上英介、柘植雅貴、内田宅郎、菅 宏美、柾木慶一、本田洋士、中原隆志、大野敦司、平賀伸彦、河岡友和、平松 憲、今村道雄、相方 浩、茶山一彰、川上広育
    • Organizer
      第51回日本肝臓学会総会(一般演題)
    • Place of Presentation
      熊本
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 当院におけるHBVキャリアのHBs抗原陰性化と肝発癌に関する検討2015

    • Author(s)
      村上英介、柘植雅貴、茶山一彰
    • Organizer
      第101回日本消化病学会総会(シンポジウム)
    • Place of Presentation
      仙台
    • Year and Date
      2015-04-16
    • Related Report
      2015 Research-status Report
  • [Presentation] 核酸アナログ先行投与によるインターフェロン反応性の変化2015

    • Author(s)
      柘植雅貴、平賀伸彦、茶山一彰
    • Organizer
      第101回日本消化病学会総会(ワークショップ)
    • Place of Presentation
      仙台
    • Year and Date
      2015-04-14
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 高力価のB型肝炎ウイルスを産生する細胞およびその作製方法2015

    • Inventor(s)
      柘植雅貴、茶山一彰
    • Industrial Property Rights Holder
      柘植雅貴、茶山一彰
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-04-10
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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