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Analysis of molecular mechanisms of new anti-virus drug against human cytomegalovirus infectious diseases

Research Project

Project/Area Number 24591492
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionHokuriku University

Principal Investigator

MURAYAMA Tsugiya  北陸大学, 薬学部, 教授 (60159184)

Co-Investigator(Kenkyū-buntansha) SADARARI Hidetaka  北陸大学, 教育能力開発センター, 助教 (60121274)
Co-Investigator(Renkei-kenkyūsha) EIZURU Yoshito  鹿児島大学, 医学部, 名誉教授 (00041351)
Research Collaborator YAMADA Rie  北陸大学, 薬学部, 助手
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsサイトメガロウイルス / トリシン / 抗ウイルス薬 / ケモカイン / STAT3 / siRNA
Outline of Final Research Achievements

It has been reported that treatment with tricin (4’,5,7-trihydroxy-3’,5’-dimethoxyflavone), a material in the rice family plants, after human cytomegalovirus (HCMV) infection significantly suppressed infectious virus production in the human embryonic fibroblast cell line (HEL). In this paper, we examined the mechanisms for the anti-HCMV activities of tricin in HEL cells. Exposure of fibroblasts to tricin inhibited infectious HCMV production, with concomitant decreases in levels of transcripts of the CXC chemokine (CXCL11) and CC chemokine (CCL2) genes. We also found that the transcripts of the HCMV immediate early (IE) gene and replication of HCMV were lower in CXCL11 and/or CCL2 gene-knockdown cells. These results suggest that tricin is a novel compound with potential anti-HCMV activity and that CXCL11 and/or CCL2 are one of the chemokines involved in HCMV replication. In addition, it is possible that CXCL11 and/or CCL2 are the one of the targets of tricin.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (31 results)

All 2015 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) Book (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] イネ科植物含有成分“Tricin”による抗ヒトサイトメガロウイルス作用機序の解明2015

    • Author(s)
      村山次哉
    • Journal Title

      New Food Industry

      Volume: 57 Pages: 24-34

    • NAID

      40020470504

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Quantitative & Qualitative Regulation of Peripheral Leukocytes Subsets plus Emotional Hormones by Floor Heating.2014

    • Author(s)
      Nobuo Yamaguchi, Amat Nurmuhammad, Jameas Zhao, Xiefeng Jia, Jiao Jian, Rui Chen, Tsugiya Murayama
    • Journal Title

      Open Journal of Reumatology & Autoimmune diseases

      Volume: 4 Issue: 02 Pages: 97-105

    • DOI

      10.4236/ojra.2014.42015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human cytomegalovirus replication supported by virus-induced activation of CCL2-CCR2 interactions.2014

    • Author(s)
      T. Murayama, M. Kikuchi, T. Miita, R. Yamada, K. Matsubara, H. Sadanari, N. Mukaida
    • Journal Title

      Biochem. Biophis. Res. Commun.

      Volume: 453 Issue: 3 Pages: 321-325

    • DOI

      10.1016/j.bbrc.2014.09.071

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Transgenic rice seed synthesizing diverse flavonoids at high levels: a new platform for flavonoid production with associated health benefits.2013

    • Author(s)
      Y. Ogo, K. Ozawa, T. Ishimaru, T. Murayama and F. Takaiwa
    • Journal Title

      Plant Biotechnol J

      Volume: 11 Pages: 734-746

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibitory Effects of Statins on Expression of Immediate-early 1 Protein of Human Cytomegalovirus in Virus-infected Cells.2013

    • Author(s)
      H. Sadanari, T. Murayama, X. Zheng, R. Yamada, K. Matsubara, H. Yoshida, T. Takahashi
    • Journal Title

      J Exp Clin Med

      Volume: 5 Pages: 187-193

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantitative regulation of peripheral leukocyte by light exercise and tailored scale for assessment.2013

    • Author(s)
      N. Yamaguchi, R.Chen, K. Okamoto, T. Takei, M. Tsubokawa, D. Sakamoto, X.-F. Jia, W. Wu, T. Murayama
    • Journal Title

      Open Journal of Immunology

      Volume: 3

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transgenic rice seed synthesizing diverse flavonoids at high levels: a new platform for flavonoid production with associated health benefits2013

    • Author(s)
      Yuko Ogo, Kenjiro Ozawa, Tsutomu Ishimaru, Tsugiya Murayama and Fumio Takaiwa
    • Journal Title

      Plant Biotechnology Journal

      Volume: XX Issue: 6 Pages: 1-13

    • DOI

      10.1111/pbi.12064

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-cytomegalovirus effects of tricin are dependent on CXCL112012

    • Author(s)
      Murayama T, Li Y, Takahashi T, Yamada R, Matsubara K, Tsuchida Y, Zheng X, Sadanari H.
    • Journal Title

      Microbes Infect

      Volume: 14 Issue: 12 Pages: 1086-1092

    • DOI

      10.1016/j.micinf.2012.05.017

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Herpes simplex virus requires PARP activity for efficient replication and induces ERK-dependent phosphorylation and ICP0-dependent nuclear localization of tankyrase 12012

    • Author(s)
      Li Z, Yamauchi Y, Kamakura M, et al
    • Journal Title

      Journal of Virology

      Volume: (In press) Issue: 1 Pages: 492-503

    • DOI

      10.1128/jvi.05897-11

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] CCL2-CCR2 dependent-human cytomegalovirus replication.2015

    • Author(s)
      Tsugiya Murayama, Marie Kikuchi, Takaki Miita, Rie Yamada, Hidetaka Sadanari, Yoshito Eizuru
    • Organizer
      . 5th International congenital CMV conference and 15th International CMV/Beta herpes virus workshop
    • Place of Presentation
      Brisbane, Australia
    • Year and Date
      2015-04-20 – 2015-04-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] TricinのCXCL11介在性抗ヒトサイトメガロウイルス作用2015

    • Author(s)
      山田理恵、定成秀貴、土田裕三、村山次哉
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] イネ科植物含有成分“Tricin”による抗ヒトサイトメガロウイルス作用機序の解明2014

    • Author(s)
      三井田隆貴、山田理恵、松原恵子、定成秀貴、村山次哉
    • Organizer
      第17回日本補完代替医療学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-01 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] Tricinの抗ヒトサイトメガロウイルス作用におけるケモカインCXCL-11の関与2014

    • Author(s)
      古谷田陽子、山田理恵、土田裕三、定成秀貴、村山次哉
    • Organizer
      第17回日本補完代替医療学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-01 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] CXC chemokin-dependent cytomegalovirus replication.2014

    • Author(s)
      Tsugiya Murayama, Hidetaka Sadanari, Ying Li, Rie Yamada, Keiko Matsubara
    • Organizer
      The 39th Annual international herpesvirus workshop
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2014-07-19 – 2014-07-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] A cell-based assay using a human cytomegalovirus (HCMV) late promoter-luciferase reporter for identifying inhibitors of HCMV replication.2014

    • Author(s)
      Hidetaka Sadanari, Rie Yamada, Keiko Matsubara, Tsugiya Murayama
    • Organizer
      The 39th Annual international herpesvirus workshop
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2014-07-19 – 2014-07-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Tricinと抗ヒトサイトメガロウイルス薬による併用効果2014

    • Author(s)
      山田理恵、定成秀貴、土田裕三、村山次哉
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトサイトメガロウイルス(HCMV)の初期―後期遺伝子と後期遺伝子のプロモーター活性を利用した抗HCMV剤検索検索システムの構築2013

    • Author(s)
      定成秀貴、長尾嘉真、三谷逸人、安井真一、山田理恵、村山次哉
    • Organizer
      第23回日本抗ウイルス療法研究会総会
    • Place of Presentation
      リーガロイヤルホテル東京
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトサイトメガロウイルス(HCMV)の初期―後期遺伝子と後期遺伝子のプロモーター活性を利用した抗HCMV剤検索検索システムの可能性2013

    • Author(s)
      定成秀貴、長尾嘉真、三谷逸人、安井真一、山田理恵、村山次哉
    • 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
    • Related Report
      2013 Research-status Report
  • [Presentation] Ganciclovirとtricin併用による抗ヒトサイトメガロウイルス作用機序の検討2013

    • Author(s)
      山田理恵、土田裕三、定成秀貴、村山次哉
    • Organizer
      第16回日本補完代替医療学会学術集会
    • Place of Presentation
      金沢勤労者プラザ
    • Related Report
      2013 Research-status Report
  • [Presentation] クマザサ含有成分“Tricin”による抗ヒトサイトメガロウイルス作用機序の検討2013

    • Author(s)
      菊池万里絵、山田理恵、定成秀貴、松原恵子、土田裕三、村山次哉
    • Organizer
      第16回日本補完代替医療学会学術集会
    • Place of Presentation
      金沢勤労者プラザ
    • Related Report
      2013 Research-status Report
  • [Presentation] Ganciclovirとtricinによる抗ヒトサイトメガロウイルス作用の検討2013

    • Author(s)
      山田理恵、須田英揮、馬場昌範、土田裕三、定成秀貴、村山次哉
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] CXCL11-dependent anti-cytomegalovirus effects of tricin2012

    • Author(s)
      Tsugiya Murayama,Ying Li, Yuuzo Tuchida, Takashi Takahashi, Rie Yamada, Hidetaka Sadanari
    • Organizer
      14th International CMV/Betaherpesvirus workshop
    • Place of Presentation
      San Francisco, CA, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Action mechanisms of tricin on anti-cytomegalovirus effect2012

    • Author(s)
      Tsugiya Murayama, Yuuzo Tuchida, Rie Yamada, Hidetaka Sadanari, Keiko Matsubara
    • Organizer
      25rd International conference on antiviral research
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] Inhibitory effects of simvastatin on human cytomegalovirus replication through altered expression of a chemokine, C-X-C motif ligand 11 in human embryonic lung cells2012

    • Author(s)
      Takashi Takahashi, Tsugiya Murayama, Ying Li, Rie Yamada, Keiko Matsubara, Xin Zheng, Hidetaka Sadanari
    • Organizer
      The 11th East Asian Conference on Infection Control and Prevention
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒトサイトメガロウイルス(HCMV)の初期―後期遺伝子と後期遺伝子のプロモーター活性を利用した抗HCMV剤検索システムの検討2012

    • Author(s)
      定成秀貴、長尾嘉真、三谷逸人、安井真一、山田理恵、村山次哉
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] Ganciclovirとtricinによる抗ヒトサイトメガロウイルス作用の相乗効果2012

    • Author(s)
      村山次哉、須田英揮、馬場昌範、土田裕三、山田理恵、定成秀貴
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒトサイトメガロウイルス(HCMV)に対する抗ウイルス剤検索に利用可能なHCMV遺伝子の検討2012

    • Author(s)
      定成秀貴、長尾嘉真、三谷逸人、安井真一、山田理恵、村山次哉
    • Organizer
      第49回日本細菌学会中部支部総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒトサイトメガロウイルスのUL100遺伝子の転写調節領域の解析

    • Author(s)
      松浦純児、定成秀貴、山田理恵、村山次哉
    • Organizer
      日本薬学会北陸支部第125回例会
    • Place of Presentation
      北陸大学薬学部
    • Related Report
      2013 Research-status Report
  • [Book] 応用細胞補完代替医療学2012

    • Author(s)
      村山次哉
    • Total Pages
      93
    • Publisher
      大学教育出版
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] トリシンアミノ酸誘導体並びにそれを含む抗ウイルス剤及び抗癌剤2012

    • Inventor(s)
      村山次哉,土田裕三、二ノ宮真之、桜井大輔 他
    • Industrial Property Rights Holder
      村山次哉,土田裕三、二ノ宮真之、桜井大輔 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-05-31
    • Acquisition Date
      2014-02-14
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 抗ウイルス剤2012

    • Inventor(s)
      村山次哉、土田裕三、渡辺邦友、纐纈守、土田康太郎、桜井大輔
    • Industrial Property Rights Holder
      村山次哉、土田裕三、渡辺邦友、纐纈守、土田康太郎、桜井大輔
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-09-16
    • Acquisition Date
      2013-01-18
    • Related Report
      2012 Research-status Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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