Screening Survey and Genotype Analysis of HTLV-1 Carrier in Asia-Pacific Region

• Project/Area Number: 19K10602
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: University of the Ryukyus
• Principal Investigator: Fukushima Takuya 琉球大学, 医学部, 教授 (40336160)
• Co-Investigator(Kenkyū-buntansha): 宮良 恵美 沖縄大学, 健康栄養学部, 准教授 (50457686)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: HTLV-1 / アジア・太平洋 / インドネシア / HIV/HTLV-1共感染 / 分布 / 遺伝子型 / アジア・太平洋地域 / キャリア調査 / genotype / ATL / HTLV-1遺伝子型 / スクリーニング調査 / バイオバンク

Outline of Research at the Start

アジア・太平洋地域（フィリピン、タイ、インドネシア、フィジー）においてHTLV-1キャリア調査を行い、HTLV-1分布状況を明らかにするとともに、生体試料をバンキングし、沖縄からアジア・太平洋に拡がるATL/HTLV-1バイオバンクを構築する。さらに、それぞれの国のHTLV-1のgenotype解析を行い、日本本土、沖縄および世界の他の地域のHTLV-1 genotypeの分布パターンと比較することにより、HTLV-1伝播経路解明の端緒を開く。

Outline of Final Research Achievements

This is the epidemiological study for HTLV-1 carrier in the Asian Pacific region. We had signed the agreement of the collaboration study of HTLV-1 screening study with Airlangga university in Indonesia on February 2020, but we had not be able to conduct the screening survey because of the COVID-19 pandemic. We had no choice but to extend the study period. In December, 2023, we conducted the test for anti-HTLV-1 antibody using the cryopreservation sera from 522 HIV carriers in the whole Indonesia. We found 3 HIV/HTLV-1 co-infection cases. All cases are originated from the residential area for the Melanesian indigenous tribes. It is presumed that the HTLV-1 genotypes are the Melanesian types (Type C). This study results show that the HTLV-1 carriers distribute not in the metropolitan ares including Jakarta and Surabaya but in the Melanesian indigenous tribe residential area in Indonesia.

Academic Significance and Societal Importance of the Research Achievements

HTLV-1は難治性疾患である成人T細胞白血病・リンパ腫、HTLV-1関連脊髄症の病因ウイルスで、感染予防対策が喫緊の課題である。そして世界の感染の現状を明らかにする研究は重要である。アジア・太平洋各国の感染状況は1980年代の調査以降の報告がなかった。今回、インドネシアの感染調査を実施し、ジャカルタ、スラバヤなど大都市部にHTLV-1キャリアは分布しておらず、オセアニア系先住民族に分布していること、さらにHIV/HTLV-1共感染例は少数であることが判明した。これはインドネシアの感染対策における保健医療へ重要な情報となる。HTLV-1感染者のDNAが保存され、バイオバンク拡大への礎となる。

Research Products

• [Journal Article] Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL. (2020)
  • Author(s): Guerrero CLH, Yamashita Y, Miyara M, Imaizumi N, Kato M, Sakihama S, Hayashi M, Miyagi T, Karimata K, Uchihara J, Ohshiro K, Todoroki J, Nakachi S, Morishima S, Karube K, Tanaka Y, Masuzaki H, Fukushima T.
  • Journal Title: Blood Adv Volume: 4 Issue: 6 Pages: 1062-1071
  • DOI: 10.1182/bloodadvances.2019001429
  • NAID: 120006937803
  • Peer Reviewed / Open Access
• [Journal Article] Conservation of a Neutralization Epitope of Human T-cell Leukemia Virus Type 1 (HTLV-1) among Currently Endemic Clinical Isolates in Okinawa, Japan (2020)
  • Author(s): Mizuguchi M, Takahashi Y, Tanaka R, Fukushima T, Tanaka Y.
  • Journal Title: Pathogens Volume: 9 Issue: 2 Pages: 82-82
  • DOI: 10.3390/pathogens9020082
  • NAID: 120006937798
  • Peer Reviewed / Open Access
• [Journal Article] EOS, an Ikaros family zinc finger transcription factor, interacts with the HTLV-1 oncoprotein Tax and is downregulated in peripheral blood mononuclear cells of HTLV-1-infected individuals, irrespective of clinical statuses. (2019)
  • Author(s): Naito T, Ushirogawa H, Fukushima T, Tanaka Y, Saito M.
  • Journal Title: Virology Journal Volume: 16 Issue: 1 Pages: 160-160
  • DOI: 10.1186/s12985-019-1270-1
  • NAID: 120006937799
  • Peer Reviewed / Open Access
• [Journal Article] Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T-cell leukemia/lymphoma. (2019)
  • Author(s): Morichika K, Karube K, Kayo H, Uchino S, Nishi Y, Nakachi S, Okamoto S, Morishima S, Ohshiro K, Nakazato I, Fukushima T, Masuzaki H.
  • Journal Title: Cancer Sci. Volume: 110 Issue: 9 Pages: 2982-2991
  • DOI: 10.1111/cas.14114
  • NAID: 120006937802
  • Peer Reviewed / Open Access
• [Journal Article] Possibility of a risk-adapted treatment strategy for untreated aggressive adult T-cell leukaemia-lymphoma (ATL) based on the ATL prognostic index: a supplementary analysis of the JCOG9801. (2019)
  • Author(s): Toyoda K, Tsukasaki K, Machida R, Kadota T, Fukushima T, Ishitsuka K, Maruyama D, Nagai H.
  • Journal Title: Br J Haematol Volume: 186 Issue: 3 Pages: 440-447
  • DOI: 10.1111/bjh.15950
  • Peer Reviewed
• [Presentation] ヒトT細胞白血病ウイルス（HTLV-1）臨床分離株における広域中和エピトープの保存 (2019)
  • Author(s): 水口真理子，高橋良明，田中礼子，福島卓也，田中勇悦
  • Organizer: 第6回日本HTLV-1学会学術総会
• [Presentation] 成人T細胞白血病・リンパ腫の病理組織診断におけるRNA in situ hybridization 法とReal-time PCR法の有用性 (2019)
  • Author(s): 高鳥光徳，崎浜秀悟，福島卓也，加留部謙之輔
  • Organizer: 第6回日本HTLV-1学会学術総会
• [Presentation] Proteomic analysis in HTLV-1 carriers and ATL patients reveals candidate biomarkers for ATL onset. (2019)
  • Author(s): Carmina Louise H. Guerrero, Yoshiko Yamashita, Megumi Kuba-Miyara, Naoki Imaizumi, Shugo Sakihama, Masaki Hayashi, Takashi Miyagi, Satoko Morishima, Kennosuke Karube, Hiroaki Masuzaki, Takuya Fukushima
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] 血清sIL-2R濃度の持続的上昇はindolent型ATLLにおける急性転化の予測に有用である (2019)
  • Author(s): 森近 一穂, 宮城 理子, 北村 紗希子, 内堀 幸恵, 友利 昌平, 花城 多恵子, 島袋 奈津紀, 玉城 啓太, 手登根 伊織, 西 由希子, 仲地 佐和子, 宮城 敬, 大城 一郁, 森島 聡子, 福島 卓也, 加留部 謙之輔, 益崎 裕章
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] ATL-Prognostic Indexを用いたATL治療戦略の提案：JCOG9801試験副次的解析 (2019)
  • Author(s): 豊田 康祐, 塚崎 邦弘, 町田 龍之介, 門田 智裕, 福島 卓也, 石塚 賢治, 丸山 大, 永井 宏和
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] Proteomic Profiling of HTLV-1 Carriers and ATL Patiernts Reveal TNFR2 As a Novel Diagnostic and Chemosensitivity Biomarker for ATL (2019)
  • Author(s): Gurrero CLH, Yamashita Y, Kuba-Miyara M, Imaizumi N, Sakihama S, Hayashi M, Miyagi T, Morishima S, Karube K, Tanaka Y, Masuzaki H, Fukushima T
  • Organizer: 61th American Society of Hematology Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] Somatic Mutations and Loss of Heterozygosity of HLA Genes Are Frequently Occurred and Tightly Associated with Poor Prognosis in Adult T Cell Leukemia-Lymphoma (2019)
  • Author(s): Tamaki K, Morishima S, Suzuki S, Shigenari A, Nomura I, Yokota Y, Morichika K, Nishi Y, Nakachi S, Okamoto S, Karube K, Fukushima T, Shiina T, Masuzaki H
  • Organizer: 61th American Society of Hematology Annual Meeting and Exposition
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] ヒトT細胞白血病ウイルス１型（HTLV-1）関連疾患の診断方法 (2019)
  • Inventor(s): 福島卓也 田中勇悦 加留部謙之輔 益崎裕章 今泉直樹
  • Industrial Property Rights Holder: 福島卓也 田中勇悦 加留部謙之輔 益崎裕章 今泉直樹
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019