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DNA damage response-related mechanisms to control intranuclear virus replication

Research Project

Project/Area Number 18H02664
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionOkayama University (2020-2021)
Osaka University (2018-2019)

Principal Investigator

Honda Tomoyuki  岡山大学, 医歯薬学域, 教授 (80402676)

Co-Investigator(Kenkyū-buntansha) 上田 啓次  大阪大学, 医学系研究科, 教授 (00221797)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsボルナウイルス / カポジ肉腫関連ヘルペスウイルス / ヒトヘルペスウイルス6型 / B型肝炎ウイルス / 免疫応答 / 細胞核 / DNA損傷 / 核 / RNAウイルス / 抗ウイルス防御 / 宿主防御機構
Outline of Final Research Achievements

In this study, we attempted to elucidate the detection and control mechanism of intranuclear-replicating viruses, which had not been elucidated. We demonstrated that there may be a common mechanism by DNA damage response (DDR) molecules that detect intranuclear-replicating viruses, but that downstream pathways that control viral replication are specific for individual viruses. It was also suggested that the signature of viral infection detected by the host is not only the viral nucleic acid itself, but also the DNA damage (or DNA damage-like) structure caused by the infection. Furthermore, we identified a novel immune response cascade against exogenous DNA. Our findings will open the way to understand immune response phenomena that have not been elucidated yet.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、これまで全く未解明であった核内増殖型ウイルスの検知・制御機構の概要が解明できたことである。ウイルス検知についてはDNA損傷修復系分子による共通機構が存在する可能性が示唆されたが、ウイルス制御については個々のウイルスに特異的であり、さらなる検討が必要であると考えられた。一方、本研究の過程で、新しい免疫応答カスケードを見出した。本研究の成果により、免疫応答についての従来の理解では説明できなかった事象の理解に繋がることが期待される。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (35 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (18 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 18 results,  Open Access: 15 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Remarks (3 results)

  • [Journal Article] Nectin-2 Acts as a Viral Entry Mediated Molecule That Binds to Human Herpesvirus 6B Glycoprotein B2022

    • Author(s)
      Ogawa Hirohito、Fujikura Daisuke、Namba Hikaru、Yamashita Nobuko、Honda Tomoyuki、Yamada Masao
    • Journal Title

      Viruses

      Volume: 14 Issue: 1 Pages: 160-160

    • DOI

      10.3390/v14010160

    • NAID

      120007188352

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Waning of Anti-SARS-CoV-2 Spike Antibody Levels 100 to 200 Days after the Second Dose of the BNT162b2 Vaccine2022

    • Author(s)
      Matsunaga Hidenori、Takeuchi Hidefumi、Oba Yuichiro、Fujimi Satoshi、Honda Tomoyuki、Tomonaga Keizo
    • Journal Title

      Vaccines

      Volume: 10 Issue: 2 Pages: 177-177

    • DOI

      10.3390/vaccines10020177

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bornavirus infection in human diseases and its molecular neuropathology2022

    • Author(s)
      Honda Tomoyuki
    • Journal Title

      Clinical and Experimental Neuroimmunology

      Volume: 13 Issue: 1 Pages: 7-16

    • DOI

      10.1111/cen3.12686

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radioligand Assay-Based Detection of Antibodies against SARS-CoV-2 in Hospital Workers Treating Patients with Severe COVID-19 in Japan2021

    • Author(s)
      Matsunaga Hidenori、Makino Akiko、Kato Yasuhiro、Murakami Teruaki、Yamaguchi Yuta、Kumanogoh Atsushi、Oba Yuichiro、Fujimi Satoshi、Honda Tomoyuki、Tomonaga Keizo
    • Journal Title

      Viruses

      Volume: 13 Issue: 2 Pages: 347-347

    • DOI

      10.3390/v13020347

    • NAID

      120007026451

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Human Endogenous Bornavirus-Like Nucleoprotein Encodes a Mitochondrial Protein Associated with Cell Viability2021

    • Author(s)
      Fujino Kan、Horie Masayuki、Kojima Shohei、Shimizu Sae、Nabekura Aya、Kobayashi Hiroko、Makino Akiko、Honda Tomoyuki、Tomonaga Keizo
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 14

    • DOI

      10.1128/jvi.02030-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A patient with human coronavirus NL63 falsely diagnosed with COVID-19; Lesson learned for the importance of definitive diagnosis2021

    • Author(s)
      Otsuka Yuki、Hagiya Hideharu、Nakano Yasuhiro、Omura Daisuke、Hasegawa Kou、Yamada Haruto、Iio Koji、Honda Tomoyuki、Otsuka Fumio
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 27 Issue: 7 Pages: 1126-1128

    • DOI

      10.1016/j.jiac.2021.05.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Traditional Chinese Medicine, Maoto, Suppresses Hepatitis B Virus Production2021

    • Author(s)
      Rahman Md. Arifur、Ueda Keiji、Honda Tomoyuki
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 10 Pages: 581345-581345

    • DOI

      10.3389/fcimb.2020.581345

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kaposi's sarcoma-associated herpesvirus is cell-intrinsically controlled in latency in microgravity.2020

    • Author(s)
      Honda T, Nakayama R, Kawahara Y, Yuge L, Ueda K.
    • Journal Title

      Virus Res.

      Volume: 276 Pages: 197821-197821

    • DOI

      10.1016/j.virusres.2019.197821

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Complete Genome Sequence of a Precore-Defective Hepatitis B Virus Genotype D2 Strain Isolated in Bangladesh2020

    • Author(s)
      Hossain Md Golzar、Mahmud Md Muket、Rahman Md Arifur、Akter Sharmin、Nazir K. H. M. Nazmul Hussain、Saha Sukumar、Wada Masami、Ohsaki Eriko、Honda Tomoyuki、Ueda Keiji
    • Journal Title

      Microbiology Resource Announcements

      Volume: 9 Issue: 11

    • DOI

      10.1128/mra.00083-20

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] T. Honda. Modeling Borna disease virus in vitro spread reveals the mode of antiviral effect conferred by an endogenous bornavirus-like element2020

    • Author(s)
      K.S. Kim, Y. Yamamoto, S. Nakaoka, K. Tomonaga, S. Iwami,
    • Journal Title

      Journal of Virology

      Volume: - Issue: 21

    • DOI

      10.1128/jvi.01204-20

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells2020

    • Author(s)
      Honda Tomoyuki、Nishikawa Yuki、Nishimura Kensuke、Teng Da、Takemoto Keiko、Ueda Keiji
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 22136-22136

    • DOI

      10.1038/s41598-020-79197-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Profiling of LINE-1-Related Genes in Hepatocellular Carcinoma2019

    • Author(s)
      Honda Tomoyuki、Rahman Md.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 3 Pages: 645-645

    • DOI

      10.3390/ijms20030645

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Latent infection with Kaposi’s sarcoma-associated herpesvirus enhances retrotransposition of long interspersed element-12019

    • Author(s)
      Nakayama Ryota、Ueno Yumiko、Ueda Keiji、Honda Tomoyuki
    • Journal Title

      Oncogene

      Volume: 印刷中 Issue: 22 Pages: 4340-4351

    • DOI

      10.1038/s41388-019-0726-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a Retroelement-Containing Human Transcript Induced in the Nucleus by Vaccination.2019

    • Author(s)
      Honda T, Takemoto K, Ueda K.
    • Journal Title

      Int J Mol Sci.

      Volume: 20(12) Issue: 12 Pages: 2875-2875

    • DOI

      10.3390/ijms20122875

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of an RNA Virus-Based Episomal Vector Capable of Switching Transgene Expression.2019

    • Author(s)
      Yamamoto Y, Tomonaga K, Honda T.
    • Journal Title

      Front Microbiol.

      Volume: 10 Pages: 2485-2485

    • DOI

      10.3389/fmicb.2019.02485

    • NAID

      120006770359

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Small Interfering RNA Cocktail Targeting the Nucleoprotein and Large Protein Genes Suppresses Borna Disease Virus Infection.2019

    • Author(s)
      Teng D, Obika S, Ueda K, Honda T.
    • Journal Title

      Front Microbiol.

      Volume: 10 Pages: 2781-2781

    • DOI

      10.3389/fmicb.2019.02781

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence of antibodies against Borna disease virus proteins in Japanese children with autism spectrum disorder.2018

    • Author(s)
      Honda T, Sofuku K, Matsunaga H, Tachibana M, Mohri I, Taniike M, Tomonaga K.
    • Journal Title

      Microbiol Immunol.

      Volume: ‐ Issue: 7 Pages: 473-476

    • DOI

      10.1111/1348-0421.12603

    • NAID

      40021602292

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of LINE-1 Retrotransposition by Capsaicin2018

    • Author(s)
      Nishikawa Yuki、Nakayama Ryota、Obika Shunsuke、Ohsaki Eriko、Ueda Keiji、Honda Tomoyuki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 10 Pages: 3243-3243

    • DOI

      10.3390/ijms19103243

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Regulation of the major immediate early gene promoter by tegument proteins of human herpesvirus-62021

    • Author(s)
      Haokun Li, Hikaru Namba, Hirohito Ogawa, Tomoyuki Honda
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒトヘルペスウイルス6Bの新規細胞侵入レセプターの探索2021

    • Author(s)
      小川 寛人, 藤倉 大輔, 難波ひかる, 山下 信子, 本田 知之, 山田 雅夫
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Epitranscriptomic regulation of Borna disease virus replication and gene expression,2021

    • Author(s)
      Teng D, Keiji Ueda, and Tomoyuki Honda
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 発がんにおけるがんウイルスとLINE-1の相互作用2021

    • Author(s)
      本田 知之
    • Organizer
      23rd Summer Retrovirus Conference
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] がん発生におけるLINE-1の役割2021

    • Author(s)
      本田 知之
    • Organizer
      第5回転移因子研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ヒトにおけるボルナウイルス感染症の実態とその病態2021

    • Author(s)
      本田 知之
    • Organizer
      第25回日本神経感染症学会総会・学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ボルナウイルス感染症の歴史と今後の展望2021

    • Author(s)
      本田 知之
    • Organizer
      令和3年ともえ会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Loss of Tropomyosin (TPM) family proteins impaired HBV production2021

    • Author(s)
      Rhaman Md. Arifur, Keiji Ueda, Tomoyuki Honda
    • Organizer
      第9回 肝炎ウイルス研修会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Screening of novel anti-HBV therapeutics.2019

    • Author(s)
      Rahman MA, Ueda K, Honda T.
    • Organizer
      第12回若手研究フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Small RNAs derived from an endogenous bornavirus element in mice suppress expression of a reporter with Borna disease virus sequences in GC2 cells.2018

    • Author(s)
      Honda T, Liu X, Garcia BC, Parrish NF, Tomonaga K.
    • Organizer
      NSV 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidation of microRNA change during borna disease virus infection.2018

    • Author(s)
      Teng D, Ueda K, Honda T.
    • Organizer
      第11回若手研究フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Dexamethasone enhances infection of Borna disease virus type 1 in mouse primary culture neuron.2018

    • Author(s)
      Kubota Y, Honda T, Saito T, Nishino Y.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Possible interaction between Kaposi’s sarcoma associated herpesvirus and retrotransposon.2018

    • Author(s)
      Nakayama R, Honda T, Ueda K.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of a BoDV vector capable of controlling the expression of foreign genes.2018

    • Author(s)
      Yamamoto Y, Honda T, Tomonaga K.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 岡山大学大学院医歯薬学総合研究科病原ウイルス学HP

    • URL

      https://www.okayama-u.ac.jp/user/virology/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 岡山大学大学院医歯薬学総合研究科病原ウイルス学HP

    • URL

      http://www.okayama-u.ac.jp/user/virology/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 大阪大学大学院医学系研究科感染症・免疫学講座ウイルス学HP

    • URL

      http://www.med.osaka-u.ac.jp/pub/virus/

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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