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Dysregulation of membrane protein expression by molecular piracy of Kaposis Sarcoma-Associated Herpesvirus

Research Project

Project/Area Number 18K06642
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

fujimuro masahiro  京都薬科大学, 薬学部, 教授 (20360927)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsヘルペスウイルス / カポジ肉腫関連ヘルペスウイルス / ユビキチン / プロテアソーム / 遺伝子発現 / シグナル伝達 / ウイルス発がん / タンパク質分解 / KSHV / カポジ肉腫 / 膜蛋白質 / FAT10 / 翻訳後修飾 / HHV-8 / p38 MAPK / 膜蛋白 / カプサイシン / 溶解感染 / ウイルス / リンパ腫 / 膜タンパク質 / 転写因子 / プロモーター / CD81 / P-gp / 発現制御
Outline of Final Research Achievements

Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 or HHV-8, was discovered as the 8th human herpesvirus. KSHV is the etiologic agent of Kaposi’s sarcoma, Castleman’s disease, and primary effusion lymphoma (PEL). We have demonstrated that KSHV downregulated cellular membrane proteins (X and Y) and the underlying molecular mechanism involved. In addition, we analyzed the mechanisms of KSHV capsid formation relating with ORF17 and KSHV lytic gene expression through the vPIC (Viral Pre-Initiation Complex) including ORF66. We obtained several novel and interesting data, and those data were reported by scientific papers. Furthermore, drug screening was performed, and we found that capsaicin, a pungent component of chili pepper, and arctigenin, a natural lignan compound found in plants of Arctium lappa, are the novel and effective drugs against PEL.

Academic Significance and Societal Importance of the Research Achievements

KSHVは健常者に感染すると深刻な疾患を起こさずにそのまま宿主に潜伏感染する。しかし、感染者の免疫不全時にKSHVはカポジ肉腫やリンパ腫(PEL)を引き起こす。KSHVの潜伏感染者の割合はアフリカでは90%以上で、日本では5-1%程度と報告されている。KSHV関連疾患のPELに関してはCHOP療法が用いられているが、有意な治療法効果は得られないことが報告されている。さらに、アシクロビルやガンシクロビルはKSHVには無効であることが知られている。よって、有効な抗KSHV薬の開発が期待されている。以上の理由により、KSHVの基礎研究とそのデータを基にした創薬研究は社会的意義を有していると言える。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (34 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 16 results,  Open Access: 9 results) Presentation (14 results) (of which Int'l Joint Research: 1 results) Remarks (3 results)

  • [Int'l Joint Research] University of California Davis(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Kaposi’s sarcoma-associated herpesvirus ORF17 plays a key role in capsid maturation.2021

    • Author(s)
      Tsurumi S, Watanabe T, Iwaisako Y, Suzuki Y, Nakano T, Fujimuro M
    • Journal Title

      Virology

      Volume: 558 Pages: 76-85

    • DOI

      10.1016/j.virol.2021.02.009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The FAT10 Posttranslational Modification Is Involved in Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus2021

    • Author(s)
      Sugimoto Atsuko、Abe Yuichi、Watanabe Tadashi、Hosokawa Kohei、Adachi Jun、Tomonaga Takeshi、Iwatani Yasumasa、Murata Takayuki、Fujimuro Masahiro
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 10 Pages: 02194-20

    • DOI

      10.1128/jvi.02194-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] UBE1a suppresses herpes simplex virus-1 replication.2021

    • Author(s)
      Ikeda M, Ito A, Sekine Y, Fujimuro M
    • Journal Title

      Viruses

      Volume: 12 Issue: 12 Pages: 1391-1391

    • DOI

      10.3390/v12121391

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Herpes simplex virus-1 infection induces ubiquitination of UBE1a.2021

    • Author(s)
      Ikeda M, Watanabe T, Ito A, Fujimuro M
    • Journal Title

      Biochemical Journal

      Volume: 478 Issue: 1 Pages: 261-279

    • DOI

      10.1042/bcj20200885

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Lysosome Pathway Degrades CD81 on the Cell Surface by Poly-ubiquitination and Clathrin-Mediated Endocytosis2020

    • Author(s)
      Hosokawa Kohei、Ishimaru Hanako、Watanabe Tadashi、Fujimuro Masahiro
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 3 Pages: 540-545

    • DOI

      10.1248/bpb.b19-01097

    • NAID

      130007804468

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-03-01
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MG132 exerts anti-viral activity against HSV-1 by overcoming virus-mediated suppression of the ERK signaling pathway.2020

    • Author(s)
      Ishimaru Hanako、Hosokawa Kohei、Sugimoto Atsuko、Tanaka Riho、Watanabe Tadashi、Fujimuro Masahiro
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 6671-6671

    • DOI

      10.1038/s41598-020-63438-1

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kaposi's sarcoma-associated herpesvirus ORF66 is essential for late gene expression and virus production via interaction with ORF34.2020

    • Author(s)
      Watanabe T, Nishimura M, Izumi T, Kuriyama K, Iwaisako Y, Hosokawa K, Takaori-Kondo A, Fujimuro M
    • Journal Title

      J. Virology

      Volume: 94 Issue: 2 Pages: 1300-1300

    • DOI

      10.1128/jvi.01300-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sulforaphane Exhibits Cytotoxic Effects against Primary Effusion Lymphoma Cells by Suppressing p38MAPK and AKT Phosphorylation2019

    • Author(s)
      Ishiura Yuki, Ishimaru Hanako, Watanabe T, Fujimuro M
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 12 Pages: 2109-2112

    • DOI

      10.1248/bpb.b19-00659

    • NAID

      130007754599

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-12-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Capsaicin Induces ATF4 Translation with Upregulation of CHOP, GADD34 and PUMA2019

    • Author(s)
      Moriguchi M, Watanabe T, Fujimuro M
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 8 Pages: 1428-1432

    • DOI

      10.1248/bpb.b19-00303

    • NAID

      130007686677

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-08-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] No enhancing effects of plasmid-specific histone acetyltransferase recruitment system on transgene expression in vivo.2019

    • Author(s)
      T Suzuki, Y Wakao, T Watanabe, M Hori, Y Ikeda, H Tsuchiya, K Kogure, M Harada-Shiba, M Fujimuro and Hiroyuki Kamiya
    • Journal Title

      Nucleosides, Nucleotides & Nucleic Acids,

      Volume: 38 Issue: 12 Pages: 942-949

    • DOI

      10.1080/15257770.2019.1638514

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and biological evaluation of novel imidazole nucleosides as potential anti-dengue virus agents2019

    • Author(s)
      Okano Yuki、Saito-Tarashima Noriko、Kurosawa Madoka、Iwabu Ai、Ota Masashi、Watanabe Tadashi、Kato Fumihiro、Hishiki Takayuki、Fujimuro Masahiro、Minakawa Noriaki
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 27 Issue: 11 Pages: 2181-2186

    • DOI

      10.1016/j.bmc.2019.04.015

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Capsaicin induces apoptosis in KSHV-pisitive primary effusion lymphoma by suppressing ERK and p38 MAPK signaling and IL-6 expression.2019

    • Author(s)
      Moriguchi M, Watanabe T, Kadota A, Fujimuro M
    • Journal Title

      Front in Oncology

      Volume: 9 Pages: 83-83

    • DOI

      10.3389/fonc.2019.00083

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Capsaicin ativates ATF-4 expression and ATF-4 dependent transcription.2019

    • Author(s)
      Moriguchi M, Watanabe T, Fujimuro M
    • Journal Title

      Bio. Pharm. Biol.

      Volume: 印刷中

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Signal transduction pathways associated with KSHV-related tumors.2018

    • Author(s)
      Watanabe T, Sugimoto A, Hosokawa k, Fujimuro M
    • Journal Title

      Adv. Exp. Med. Biol.

      Volume: 1045 Pages: 321-355

    • DOI

      10.1007/978-981-10-7230-7_15

    • ISBN
      9789811072291, 9789811072307
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] KSHV episomes reveal dynamic chromatin loop formation with domain specific gene regulation.2018

    • Author(s)
      Campbell M*, Watanabe T*, Nakano K*, Davis RR, Lyu Y, Tepper CG, Durbin-Johnson B, Fujimuro M, Izumiya Y.
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 49-49

    • DOI

      10.1038/s41467-017-02089-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] New diterpenes from Nigella damascena seeds and their antiviral activities against herpes simplex virus type-12018

    • Author(s)
      Ogawa Keiko、Nakamura Seikou、Hosokawa Kohei、Ishimaru Hanako、Saito Natsuki、Ryu Kaori、Fujimuro Masahiro、Nakashima Souichi、Matsuda Hisashi
    • Journal Title

      Journal of Natural Medicines

      Volume: 72 Issue: 2 Pages: 439-447

    • DOI

      10.1007/s11418-017-1166-6

    • NAID

      40021511325

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ピリジニウム型フラーレン誘導体はウイルス感染リンパ腫に対する細胞増殖を抑制する2020

    • Author(s)
      門田彩乃, 森口美里, 渡部匡史, 関根勇一, 中村成夫, 安野拓実, 大江知之, 増野匡彦, 藤室雅弘
    • Organizer
      第70回日本薬学会関西支部大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 単純ヘルペスウイルス1型感染時におけるユビキチン活性化酵素 UBE1のユビキチン化修飾の機能解析2020

    • Author(s)
      池田茉莉那, 伊藤昭博, 渡部匡史, 藤室雅弘
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] プロテアソーム阻害薬MG132は単純ヘルペスウイルスによるERKシグナル抑制を阻害することで抗ウイルス活性を示す2020

    • Author(s)
      石丸華子, 細川晃平, 杉本温子, 田中里歩, 渡部匡史, 藤室雅弘
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] カポジ肉腫関連ヘルペスウイルスがコードするORF17のプロテアーゼ活性は,ウイルス成熟カプシド形成に必須である2019

    • Author(s)
      鶴見さやか, 渡部匡史, 鈴木陽一, 中野隆史, 藤室雅弘
    • Organizer
      日本薬学会第139年会
    • Related Report
      2019 Research-status Report
  • [Presentation] カポジ肉腫関連ヘルペスウイルス遺伝子ORF7のウイルス複製時における機能解析2019

    • Author(s)
      祝迫佑紀, 渡部匡史, 藤室雅弘
    • Organizer
      日本薬学会第139年会
    • Related Report
      2019 Research-status Report
  • [Presentation] KSHV感染はSnailの安定化を介して上皮間葉転換を促進する2019

    • Author(s)
      花尻美月, 寺尾友岐, 松本遼太郎, 渡部匡史, 藤室雅弘
    • Organizer
      日本薬学会第139年会
    • Related Report
      2019 Research-status Report
  • [Presentation] カポジ肉腫関連ヘルペスウイルスがコードするLANAはがん遺伝子産物ELLを安定化する2019

    • Author(s)
      吉澤想大, 中村甚弥, 渡部匡史, 藤室雅弘
    • Organizer
      日本薬学会第139年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ピリジニウム型フラーレン誘導体のウイルス感染リンパ腫に対する抗腫瘍活性2019

    • Author(s)
      門田彩乃, 森口美里, 渡部匡史, 中村茂夫, 安野拓美, 大江知之, 増野匡彦, 藤室 雅弘
    • Organizer
      日本薬学会第139年会
    • Related Report
      2019 Research-status Report
  • [Presentation] カポジ肉腫関連ヘルペスウイルス遺伝子ORF66は、ウイルス性転写開始前複合体因子として機能する2019

    • Author(s)
      渡部匡史, 藤室雅弘
    • Organizer
      第60回日本臨床ウイルス学会
    • Related Report
      2019 Research-status Report
  • [Presentation] カポジ肉腫関連ヘルペスウイルスのコードするウイルス性プロテアーゼ ORF17 はウイルス産生に必須である2018

    • Author(s)
      田中美和, 渡部匡史, 藤室雅弘
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Research-status Report
  • [Presentation] カポジ肉腫関連ヘルペスウイルスがコードするORF28の機能解析2018

    • Author(s)
      鶴見さやか, 渡部匡史, 藤室雅弘
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Research-status Report
  • [Presentation] B型肝炎ウイルス由来ウイルス様粒子(HBV-VLP)の精製法の確立2018

    • Author(s)
      大川浩史, 石田真紗子, 細川晃平, 渡部匡史, 上田啓次, 藤室雅弘
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Kpoosi’s Sarcoma-Associated Her4pesvirus ORD66 is Essential for Virus Production and Late Gene Expression2018

    • Author(s)
      Tadashi Watanabe, Mayu Nishimura, Kazushi Kuriyama, Aya Hashimoto, Kouhei Hosokawa, Mel Campbell, Ryan Davis, Clifford G. Tepper, Yoshihiro Izumiya, Masahiro Fujimuro
    • Organizer
      International Conference on EBV & KSHV
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 溶解感染におけるユビキチン様タンパクFAT10関連タンパクの機能解析2018

    • Author(s)
      杉本温子, 渡部匡史, 阿部雄一, 足立淳, 藤室雅弘
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Remarks] 京都薬科大学 細胞生物学分野webページ

    • URL

      https://labo.kyoto-phu.ac.jp/cellbiology/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 京都薬科大学 細胞生物学分野

    • URL

      http://labo.kyoto-phu.ac.jp/cellbiology/

    • Related Report
      2019 Research-status Report
  • [Remarks] 細胞生物学分野

    • URL

      http://labo.kyoto-phu.ac.jp/cellbiology/

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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