Dynamic evolution and different pathogenesis of HTLV-1 across multiple continents revealed by next generation sequencing technology

• Project/Area Number: 18KK0230
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Kumamoto 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): 上野 貴将 熊本大学, ヒトレトロウイルス学共同研究センター, 教授 (10322314) ; 勝屋 弘雄 佐賀大学, 医学部, 助教 (80632041)
• Project Period (FY): 2018-10-09 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2020: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: HTLV-1 / 国際共同研究 / HTLV-1感染症

Outline of Final Research Achievements

We performed international collaborative research for HTLV-1 infection by forming a global network. First, we have analyzed HTLV-1 provirus in Japan. We characterized 100 infected individuals and determined whole proviral sequence by using DNA-capture-seq and published the result in Cell Reports 2019. Second, we analyzed serum from HIV-1-infected individuals in Tanzania and found there was no HTLV-1 positive individuals. Third, we worked with Prof Mangano in Argentina in South American continent, but the study is now stopped due to COVID-19. Fourth, we collaborated with researchers in UK and analyzed HIV/HTLV coinfected individuals. We have found that the PVL of both HIV-1 and HTLV-1 in coinfected individuals was significantly higher than that of the respective virus in mono-infected individuals. The degree of oligoclonality of both HIV-1- and HTLV-1-infected cells in co-infected individuals was also greater than that in mono-infected subjects. The study has been published in JID 2021.

Academic Significance and Societal Importance of the Research Achievements

得られた意義を以下に列挙する。①日本の約１００症例の感染者のHTLV-1プロウイルスの完全長を解析し、今後のHTLV-1研究推進に資するデータを報告した。②中央アフリカ地域ではHTLV-1感染者が多いと予想したが、タンザニアで294名調べ、陽性者無しとの結果であった。アフリカの中でも地域差が大きいと考えられた。③HIV-1, HTLV-1二重感染者検体解析を行い、単感染者に比べて感染細胞の割合が高いことを見出した。１つのメカニズムとしてウイルス組み込み部位の分布が異なっている事を示した。HIV-1, HTLV-1二重感染者におけるウイルス制御に向けた１つの基礎的データになると考えられた。

Research Products

• [Int'l Joint Research] Imperial/Glasgow(英国)
• [Int'l Joint Research] Muhimbili University(タンザニア)
• [Int'l Joint Research] Dr. Juan P. Garrahan Pediatric Hospital(アルゼンチン)
• [Int'l Joint Research] リヨン大学(フランス)
• [Int'l Joint Research] imperial college/グラスゴー大学(英国)
• [Int'l Joint Research] Dr. Juan P. Garrahan Pediatric Hospital(アルゼンチン)
• [Int'l Joint Research] Muhimbili大学(タンザニア)
• [Int'l Joint Research] ケープタウン大学(南アフリカ)
• [Int'l Joint Research] Dr. Juan P. Garrahan Pediatric Hospital(アルゼンチン)
• [Int'l Joint Research] インペリアル大学(英国)
• [Int'l Joint Research] Muhimbili大学(タンザニア)
• [Journal Article] Clonality of HIV-1 and HTLV-1 infected cells in naturally coinfected individuals (2021)
  • 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
  • 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 SNP (2021)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Human Leukocyte Antigen-Associated Polymorphisms on Variability of HIV-1 Accessory and Regulatory Proteins (2021)
  • Author(s): Kamori Doreen、Hasan Zafrul、Carlson Jonathan、Kawana-Tachikawa Ai、Gatanaga Hiroyuki、Oka Shinichi、Ueno Takamasa
  • Journal Title: AIDS Research and Human Retroviruses Volume: - Issue: 12 Pages: 962-966
  • DOI: 10.1089/aid.2021.0055
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] T-cell dysregulation in COVID-19 (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Blood and lymphatic systems are segregated by the FLCN tumor suppressor (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In?Vivo (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] An HIV-1 Nef genotype that diminishes immune control mediated by protective human leucocyte antigen alleles (2020)
  • Author(s): Mwimanzi Francis、Ngare Isaac、Toyoda Mako、Mori Masahiko、Mann Jaclyn、Ndung’u Thumbi、Goulder Phillip、Ueno Takamasa
  • Journal Title: AIDS Volume: 34 Issue: 9 Pages: 1325-1330
  • DOI: 10.1097/qad.0000000000002559
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circulating HIV-1 Integrase Genotypes in Tanzania: Implication on the Introduction of Integrase Inhibitors-Based Antiretroviral Therapy Regimen (2020)
  • Author(s): Masoud Salim、Kamori Doreen、Barabona Godfrey、Mahiti Macdonald、Sunguya Bruno、Lyamuya Eligius、Ueno Takamasa
  • Journal Title: AIDS Research and Human Retroviruses Volume: - Issue: 6 Pages: 539-543
  • DOI: 10.1089/aid.2020.0021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] HTLV-1 contains a high CG dinucleotide content and is susceptible to the host antiviral protein ZAP (2019)
  • Author(s): Miyazato Paola、Matsuo Misaki、Tan Benjy J. Y.、Tokunaga Michiyo、Katsuya Hiroo、Islam Saiful、Ito Jumpei、Murakawa Yasuhiro、Satou Yorifumi
  • Journal Title: Retrovirology Volume: 16 Issue: 1 Pages: 38-38
  • DOI: 10.1186/s12977-019-0500-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach (2019)
  • Author(s): Katsuya H, Islam S, Tan, Ito J, Miyazato P, Matsuo, Inada Y, Iwase, Uchiyama Yoshikazu、Hata Hiroyuki、Sato T, Yagishita N, Araya N, Ueno T, Nosaka K, Tokunaga M, Yamagishi M, Watanabe T, Uchimaru K, Fujisawa J-i, Utsunomiya A, Yamano Y, Satou Y
  • Journal Title: Cell Reports Volume: 29 Issue: 3 Pages: 724-735
  • DOI: 10.1016/j.celrep.2019.09.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HIV-1 DNA-capture-seq is a useful tool for the comprehensive characterization of HIV-1 provirus (2019)
  • Author(s): Iwase Saori C.、Miyazato Paola、Katsuya Hiroo、Islam Saiful、Yang Benjy Tan Jek、Ito Jumpei、Matsuo Misaki、Takeuchi Hiroaki、Ishida Takaomi、Matsuda Kouki、Maeda Kenji、Satou Yorifumi
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 12326-12326
  • DOI: 10.1038/s41598-019-48681-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TFE3 Xp11.2 translocation renal cell carcinoma mouse model reveals novel therapeutic targets and identifies GPNMB as a diagnostic marker for human disease. (2019)
  • Author(s): Baba M, Furuya M, Motoshima T, Lang M, Funasaki S, Ma W, Sun HW, Hasumi H, Huang Y, Kato I, Kadomatsu T, Satou Y, Morris N, Karim BO, Ileva L, Kalen JD, Wilan Krisna LA, Hasumi Y, Sugiyama A, Kurahashi R, Nishimoto K, Oyama M, Nagashima Y, Kuroda N, Araki K, Eto M, Yao M, Kamba T, Suda T, Oike Y, Schmidt LS, Linehan WM
  • Journal Title: Molecular Cancer Research Volume: 印刷中 Issue: 8 Pages: 1613-1626
  • DOI: 10.1158/1541-7786.mcr-18-1235
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 「HTLV-1感染細胞クローン選択におけるウイルス組み込み部位の意義 ;レトロウイルスHTLV-1とヒトゲノムの相互作用に関する最近の話題」 (2019)
  • Author(s): 松尾美沙希、宮里パオラ、佐藤賢文
  • Journal Title: ウイルス Volume: 第69巻
  • NAID: 130007905317
• [Journal Article] Epigenetic changes around the pX region and spontaneous HTLV-1 transcription are CTCF-independent. (2018)
  • Author(s): Miura Michi; Miyazato Paola; Satou Yorifumi; Tanaka Yuetsu; Bangham Charles RM.
  • Journal Title: Wellcome Open Res Volume: - Pages: 105-105
  • DOI: 10.12688/wellcomeopenres.14741.2
  • NAID: 120006849702
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Phosphatidylinositol 3-kinase-δ (PI3K-δ) is a potential therapeutic target in adult T-cell leukemia-lymphoma (2018)
  • Author(s): Katsuya Hiroo、Cook Lucy B. M.、Rowan Aileen G.、Satou Yorifumi、Taylor Graham P.、Bangham Charles R. M.
  • Journal Title: Biomarker Research Volume: 6 Issue: 1 Pages: 24-24
  • DOI: 10.1186/s40364-018-0138-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Elucidation of HTLV-1 pathogenesis by single cell approach (2021)
  • Author(s): Satou Y
  • Organizer: Virtual Mini Symposium on HTLV-1 Leukemogenesis
  • 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
  • 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
• [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
  • Invited
• [Presentation] Exploration of T-cell Landscape in HTLV-1 Infection by Massive Single Cell Transcriptomics (2020)
  • 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
  • Int'l Joint Research
• [Presentation] Investigation of HIV-1 latency mechanisms in THP-1 cells harbouring intact HIV-1 provirus (2020)
  • Author(s): Rahman A, Ninomiya N, Matsuo M, Takeuchi H, Sugata K, Satou Y
  • Organizer: 21st Kumamoto AIDS Seminar
• [Presentation] Utilizing ‘Tocky’ system for elucidating HIV-1 provirus dynamics and transcriptional determinants (2020)
  • 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
• [Presentation] 1.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 (2019)
  • Author(s): 佐藤賢文
  • Organizer: 日本臨床ウイルス学会
  • Invited
• [Presentation] ウイルスDNA-capture-seqによるHTLV-1感染者プロウイルスの網羅的解析 (2019)
  • Author(s): 佐藤賢文
  • Organizer: 生命科学4プラットフォーム 説明会・成果シンポジウム
• [Presentation] 8.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について (2019)
  • Author(s): 佐藤賢文
  • Organizer: 第6回日本HTLV-1学会学術集会
• [Presentation] 13.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 (2019)
  • Author(s): 佐藤賢文
  • Organizer: 第56回日本ウイルス学会九州支部総会
  • Invited
• [Presentation] 単一細胞分析データマイニングによるHTLV-1持続潜伏感染機構の解明 (2019)
  • Author(s): 佐藤賢文
  • Organizer: HTLV-1 関連疾患研究領域 研究班合同発表会
  • Invited
• [Presentation] 21.The nature of HTLV-1 provirus in naturally infected individuals analyzed by the viral DNA-capture-seq approach (2019)
  • Author(s): Islam S, Katsuya H,et al
  • Organizer: 19th International Conference on Human Retrovirology: HTLV and Related Viruses
  • Int'l Joint Research
• [Presentation] 23.First Argentinean HTLV-1 complete genomes with their integration sites using NGS technologies. (2019)
  • Author(s): Maria Pineda, et al
  • Organizer: 19th International Conference on Human Retrovirology: HTLV and Related Viruses
  • Int'l Joint Research
• [Presentation] 24.Possible role of ZC3HAV1 protein in the post-transcriptional regulation of HTLV-1 RNAs (2019)
  • Author(s): Miyazato P, Tan BJY, Tokunaga M, Katsuya H, Matsuo M, Ito J, Murakawa Y, Satou Y.
  • Organizer: 19th International Conference on Human Retrovirology: HTLV and Related Viruses
  • Int'l Joint Research
• [Presentation] Identification and Molecular Characterization of a New HTLV-1 Enhancer (2019)
  • Author(s): Misaki Matsuo, Takaharu Ueno, Paola Miyazato, Hiroo Katsuya, Saiful Islam, Benjy Tan, Saori Iwase, Masahito Tokunaga, Kisato Nosaka, Atae Utsunomya, Jun-ichi Fujisawa, Yorifumi Satou，
  • Organizer: 19th International Conference on Human Retrovirology: HTLV and Related Viruses
  • Int'l Joint Research
• [Presentation] 29.The presence and possible role of virus-host chimeric transcripts in adult T-cell leukemia-lymphoma. (2019)
  • Author(s): Katsuya H, Miyazato P, Islam S, Tan BJY, Inada Y, Matsuo M, Ueno T, Tokunaga M, Hata H, Yamagishi M, Fujisawa J, Watanabe T, Uchimaru K, Utsunomiya A, Kimura S, Satou Y.
  • Organizer: 62nd Annual Meeting of American Society of Hematology
  • Int'l Joint Research
• [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解析 (2019)
  • Author(s): 佐藤賢文
  • Organizer: 第4回鹿児島大学感染症制御のためのシンポジウム
• [Presentation] 単一細胞分析データマイニングによるHTLV-1持続潜伏感染機構の解明 (2019)
  • Author(s): 佐藤賢文
  • Organizer: 平成30年度HTLV-1関連疾患研究領域研究班合同発表会
  • Invited
• [Presentation] 次世代DNAシークエンス技術を活用したウイルス研究 (2019)
  • Author(s): 佐藤賢文
  • Organizer: 第66回日本生態学会大会
• [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 (2019)
  • Author(s): 佐藤賢文
  • Organizer: 【AMED新興再興】新興再興感染症制御PJ（3事業）合同シンポジウム
• [Presentation] Massive single cell profiling of peripheral blood from human T-cell leukemia virus infected individuals (2018)
  • Author(s): 佐藤賢文
  • Organizer: KAIST-KUシンポジウム
• [Presentation] Molecular Characterization of a New HTLV-1 Enhancer. - HTLV-1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 (2018)
  • Author(s): 松尾美沙希、上野孝治、宮里パオラ、勝屋弘雄、徳永雅仁、野坂生郷、宇都宮與、藤澤順一、佐藤賢文
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] HTLV-1-infected Asymptomatic Carriers versus ATL PBMCs: A Single-Cell Transcriptional Profiling Approach (2018)
  • Author(s): Benjy Tan Jek Yang, Katsuya Hiroo, Miyazato Paola, Uchiyama Yoshikazu, Sakurai Yasushi, Satou Yorifumi
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] Possible role of ZC3HAV1 protein in the post-transcriptional regulation of HTLV-1 RNAs (2018)
  • Author(s): Paola Miyazato, Benjy Tan Jek Yang, Michiyo Tokunaga, Hiroo Katsuya, Misaki Matsuo, Junpei Ito, Yasuhiro Murakawa, Yorifumi Satou
  • Organizer: 第19回熊本エイズセミナ―
• [Presentation] Establishment of a Sensitive Detection Method for a Study on the Possible Role of Virus-Host Chimeric Transcripts in Maintaining the Latent Reservoir (2018)
  • Author(s): Benjy Tan Jek Yang, Saori Iwase, Hiroo Katsuya, Paola Miyazato, Mohammad Saiful Islam, Kenji Maeda, Shuzo Matsushita, Yorifumi Satou
  • Organizer: 第19回熊本エイズセミナ―
• [Presentation] Possible role of ZC3HAV1 protein in the post-transcriptional regulation of HTLV-1 RNAs－HTLV-1 RNAの転写後調整におけるZC3HAV1タンパク質の役割 (2018)
  • Author(s): Paola Miyazato, Benjy Tan Jek Yang, Michiyo Tokunaga, Hiroo Katsuya, Misaki Matsuo, Junpei Ito, Yasuhiro Murakawa, Yorifumi Satou,
  • Organizer: 第41回日本分子生物学会年会
• [Remarks] 熊本大学 国際先端医学研究機構 エイズ学研究センター佐藤研究室_「RESEARCH」
  • URL: http://www.caids.kumamoto-u.ac.jp/satou/research.html