• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of HTLV-1 pathogenesis by multidirectional and high-resolution research technique with longitudinal clinical samples

Research Project

Project/Area Number 20H03724
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionKumamoto University

Principal Investigator

SATOU YORIFUMI  熊本大学, ヒトレトロウイルス学共同研究センター, 教授 (70402807)

Co-Investigator(Kenkyū-buntansha) 末岡 榮三朗  佐賀大学, 医学部, 教授 (00270603)
梅北 邦彦  宮崎大学, 医学部, 准教授 (20506084)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords慢性持続ウイルス感染症 / HTLV-1 / ATL / HAM / HTLV-1感染症 / single cell analysis / 成人T細胞白血病リンパ腫 / 慢性関節リウマチ / ウイルス特異的CTL / 抗ウイルス免疫応答 / リウマチ関節 / 免疫抑制剤
Outline of Research at the Start

本研究は、先端的技術を活用して経時的なHTLV-1感染者検体(主に無症候性感染者とHTLV-1感染者リウマチ関節患者)を多角的かつ高精度に解析を行うことで、HTLV-1病原性発現メカニズムの解明を目指す。申請者らが最近確立した高精度かつ網羅的なプロウイルス解析技術を活用する。抗ウイルス免疫応答に関して、ELISpotや抗体価測定、フローサイトメトリー解析、更に一部の症例に関しては、シングルセルRNA-seq解析を行う事で詳細な観察を行う。以上により、感染細胞のクローン性増殖機序やリウマチ関節炎症病態における機能について明らかにすることを目的とする。

Outline of Final Research Achievements

We have been collecting clinical sample and information in the clinic in Saga and Miyazaki University hospital. We also analyze status of HTLV-1 infection by using HAS-flow. We observed high background signal in Tb assay in HTLV-1 positive RA patients. We identified that the reason may be immune response against HTLV-1 antigen during the Tb test. We also performed single cell analysis using PBMCs from asymptomatic carriers and ATL patients. We published the study result in JCI 2022. Further research would be required to elucidate pathogenesis of HTLV-1 infection.

Academic Significance and Societal Importance of the Research Achievements

HTLV-1は様々な細胞種に感染するものの腫瘍化する細胞はCD4+T細胞である。シングルセルデータ解析によって、HTLV-1によるT細胞腫瘍化のプロセスを可視化することに成功し、ウイルスがん化メカニズムの一端を明らかにすることが出来た。早期発症予防法の確立に向けた基盤となるデータ取得が行われた。また、HTLV-1陽性のリウマチ患者の臨床情報、検体収集、T spot検査異常に関する知見を深めることが出来た。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (35 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (4 results) Journal Article (12 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (17 results) (of which Int'l Joint Research: 8 results,  Invited: 9 results) Remarks (2 results)

  • [Int'l Joint Research] Imperial College(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] The Ohio State University(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Imperial 大学(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Imperial大学(英国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Clone Dynamics and Its Application for the Diagnosis of Enzootic Bovine Leukosis2023

    • Author(s)
      Hossain Md Belal、Kobayashi Tomoko、Makimoto Sakurako、Matsuo Misaki、Nishikaku Kohei、Tan Benjy Jek Yang、Rahman Akhinur、Rajib Samiul Alam、Sugata Kenji、Ohnuki Nagaki、Saito Masumichi、Inenaga Toshiaki、Imakawa Kazuhiko、Satou Yorifumi
    • Journal Title

      Journal of Virology

      Volume: 97 Issue: 1

    • DOI

      10.1128/jvi.01542-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HTLV-1 intragenic viral enhancer influences immortalization phenotype in vitro, but is dispensable for persistence and disease development in animal models2022

    • Author(s)
      Maksimova Victoria、Smith Susan、Seth Jaideep、Phelps Cameron、Niewiesk Stefan、Satou Yorifumi、Green Patrick L.、Panfil Amanda R.
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 954077-954077

    • DOI

      10.3389/fimmu.2022.954077

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification and characterization of a novel enhancer in the HTLV-1 proviral genome2022

    • Author(s)
      Matsuo Misaki、Ueno Takaharu、Monde Kazuaki、Sugata Kenji、Tan Benjy Jek Yang、Rahman Akhinur、Miyazato Paola、Uchiyama Kyosuke、Islam Saiful、Katsuya Hiroo、Nakajima Shinsuke、Tokunaga Masahito、Nosaka Kisato、Hata Hiroyuki、Utsunomiya Atae、Fujisawa Jun-ichi、Satou Yorifumi
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 2405-2405

    • DOI

      10.1038/s41467-022-30029-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HTLV-1 persistence and leukemogenesis: A game of hide-and-seek with the host immune system2022

    • Author(s)
      Tan Benjy J. Y.、Sugata Kenji、Ono Masahiro、Satou Yorifumi
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 01-12

    • DOI

      10.3389/fimmu.2022.991928

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A SARS-CoV-2 Delta variant containing mutation in the probe binding region used for RT-qPCR test in Japan exhibited atypical PCR amplification and might induce false negative result2022

    • Author(s)
      Rajib Samiul Alam、Ogi Yasuhiro、Hossain Md Belal、Ikeda Terumasa、Tanaka Eiichi、Kawaguchi Tatsuya、Satou Yorifumi
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 28 Issue: 5 Pages: 669-677

    • DOI

      10.1016/j.jiac.2022.01.019

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1 infection promotes excessive T cell activation and transformation into adult T cell leukemia/lymphoma2021

    • Author(s)
      Tan Benjy J.Y.、Sugata Kenji et al.
    • Journal Title

      Journal of Clinical Investigation

      Volume: 131 Issue: 24

    • DOI

      10.1172/jci150472

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clonality of HIV-1 and HTLV-1 infected cells in naturally coinfected individuals2021

    • Author(s)
      Katsuya H, Cook L, Rowan AG, Melamed A, Turpin J, Ito J, Islam S, Miyazato P, Tan B, Matsuo M, Miyakawa T, Nakata H, Matsushita S, Taylor GP, Bangham CRM, Kimura S, Satou Y.
    • Journal Title

      The Journal of Infectious Diseases

      Volume: 0 Issue: 2 Pages: 0-0

    • DOI

      10.1093/infdis/jiab202

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A target enrichment high throughput sequencing system for characterization of BLV whole genome sequence, integration sites, clonality and host SNP2021

    • Author(s)
      Ohnuki N, Kobayashi T, Matsuo M, Nishikaku K, Kusama K, Torii Y, Inagaki Y, Hori M, Imakawa K, Satou Y
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 4521-4521

    • DOI

      10.1038/s41598-021-83909-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] T-cell dysregulation in COVID-192020

    • Author(s)
      Kalfaoglu B, Almeida-Santos J, Tye CA, Satou Y, Ono M
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 538 Pages: 204-210

    • DOI

      10.1016/j.bbrc.2020.10.079

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Blood and lymphatic systems are segregated by the FLCN tumor suppressor2020

    • Author(s)
      Tai-Nagara I, Hasumi Y, Kusumoto D, Hasumi H, Okabe K, Ando T, Matsuzaki F, Itoh F, Saya H, Liu C, Li W, Mukouyama Y, Linehan WM, Liu X, Hirashima M, Suzuki Y, Funasaki S, Satou Y, Furuya M, Baba M, Kubota Y.
    • Journal Title

      Nat. Commun.

      Volume: 11 Issue: 1 Pages: 6314-6314

    • DOI

      10.1038/s41467-020-20156-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis2020

    • Author(s)
      Kalfaoglu B, Almeida-Santos J, Tye A C, Satou Y, Ono M
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 589380-589380

    • DOI

      10.3389/fimmu.2020.589380

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In?Vivo2020

    • Author(s)
      Aso Hirofumi、Nagaoka Shumpei、Kawakami Eiryo、Ito Jumpei、Islam Saiful、Tan Benjy Jek Yang、Nakaoka Shinji、Ashizaki Koichi、Shiroguchi Katsuyuki、Suzuki Yutaka、Satou Yorifumi、Koyanagi Yoshio、Sato Kei
    • Journal Title

      Cell Reports

      Volume: 32 Issue: 2 Pages: 107887-107887

    • DOI

      10.1016/j.celrep.2020.107887

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] シングルセル解析による HTLV-1 感染病態メカニズム解明研究2023

    • Author(s)
      佐藤 賢文
    • Organizer
      和4年度「感染・免疫・がん・炎症」全国共同研究拠点シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 「Advanced sequencing technologies reveal new insights into oncogenic mechanism induced by HTLV-1」2022

    • Author(s)
      Yorifumi Satou
    • Organizer
      The 20th International Conference on Human Retrovirology HTLV and related viruses
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 「HTLV-1 infection promotes excessive T cell activation and transformation into adult T cell leukemia / lymphoma」2022

    • Author(s)
      Benjy Jek Yang Tan, Satou Y
    • Organizer
      The 20th International Conference on Human Retrovirology HTLV and related viruses
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「Simplified detection method for the clonality of Bovine leukemia virus-infected cells and early diagnosis of Enzootic Bovine Leukosis」2022

    • Author(s)
      Md Belal Hossain, Yorifumi Satou
    • Organizer
      The 20th International Conference on Human Retrovirology HTLV and related viruses
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Single cell analysis to elucidate mechanisms underlying oncogenesis and chronic inflammation caused by HTLV-12022

    • Author(s)
      Yorifumi Satou
    • Organizer
      Oxford-Kumamoto Universities Joint Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 感染者体内における感染細胞動態に関する考察~ウイルス抗原発現と抗ウイルス免疫との均衡~2022

    • Author(s)
      佐藤 賢文
    • Organizer
      第8回日本HTLV-1学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Immune profiling of HTLV-1-specific CTLs in peripheral blood and cerebrospinal fluid of HAM/TSP patients for novel biomarker discovery2022

    • Author(s)
      Benjy Jek Yang Tan, Satou Y
    • Organizer
      Single Cell Genomics 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Single cell analysis to elucidate mechanisms underlying oncogenesis caused by HTLV-12022

    • Author(s)
      佐藤 賢文
    • Organizer
      第20回あわじ感染と免疫国際フォーラム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] ヒト T 細胞白血病ウイルスによるウイルス病原性発現メカニズム -シングルセル研究による新たな展開-2022

    • Author(s)
      佐藤 賢文
    • Organizer
      フォーラム2022 衛生薬学・環境トキシコロジー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Elucidation of HTLV-1 pathogenesis by single cell approach.2021

    • Author(s)
      佐藤賢文
    • Organizer
      UK-Japan Zoom symposium on HTLV-1 leukemogenesis.
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Elucidation of HTLV-1 pathogenesis by single cell approach2021

    • Author(s)
      Satou Y
    • Organizer
      Virtual Mini Symposium on HTLV-1 Leukemogenesis
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] HTLV-1 感染病態解明へ向けた感染者血液のシングルセルトランスクリプトーム解析2020

    • Author(s)
      佐藤 賢文
    • Organizer
      日本生体防御学会学術総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] HTLV-1プロウイルス内に存在する新規エンハンサー領域の分子メカニズム解析2020

    • Author(s)
      松尾美沙希、Benjy Tan Jek Yang、佐藤賢文
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] HTLV-1プロウイルスにおける新規エンハンサーの特定と分子メカニズム解析2020

    • Author(s)
      松尾美沙希
    • Organizer
      ウイルス学若手研究集会2020
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Exploration of T-cell Landscape in HTLV-1 Infection by Massive Single Cell Transcriptomics2020

    • Author(s)
      Tan BYJ, Sugata K, Reda O, Matsuo M, Uchiyama K, Ono M, Satou Y
    • Organizer
      Frontiers in Single Cell Genomics (Virtual), Cold Spring Harbor Asia
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Investigation of HIV-1 latency mechanisms in THP-1 cells harbouring intact HIV-1 provirus2020

    • Author(s)
      Rahman A, Ninomiya N, Matsuo M, Takeuchi H, Sugata K, Satou Y
    • Organizer
      21st Kumamoto AIDS Seminar
    • Related Report
      2020 Annual Research Report
  • [Presentation] Utilizing ‘Tocky’ system for elucidating HIV-1 provirus dynamics and transcriptional determinants2020

    • Author(s)
      Reda O, Monde K, Sugata K, Rahman A, Tan BYJ, Matsuo M, Ono M, Takeuchi H, Satou Y
    • Organizer
      21st Kumamoto AIDS Seminar
    • Related Report
      2020 Annual Research Report
  • [Remarks]

    • URL

      https://kumamoto-u-jrchri.jp/satou/achievements/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      https://kumamoto-u-jrchri.jp/satou/

    • Related Report
      2021 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi