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Research toward elimination of HIV persistent infected cells remaining under antiretroviral therapy (ART)

Research Project

Project/Area Number 15H04870
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Infectious disease medicine
Research InstitutionKumamoto University

Principal Investigator

Matsushita Shuzo  熊本大学, エイズ学研究センター, 教授 (00199788)

Co-Investigator(Kenkyū-buntansha) 佐藤 賢文  熊本大学, エイズ学研究センター, 教授 (70402807)
Co-Investigator(Renkei-kenkyūsha) KUWATA Takeo  熊本大学, エイズ学研究センター, 特任講師 (70346063)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords感染症治療学 / 感染症防御学 / ウイルス / 内科 / 感染症
Outline of Final Research Achievements

HIV-1 infected cells persisting under antiretroviral therapy (ART) are targets for therapeutic development for the cure of HIV-1 infection. We investigated the kinetics of proviral DNA (pDNA) using qPCR for 840 specimens of peripheral blood mononuclear cells (PBMC) of 59 cases under long-term treatment from 1996. When untreated, pDNA was 284 copies on average per million PBMCs, but it decreased with ART initiation. On the other hand, in the course of long-term treatment, pDNA plateaued at a certain level that varies from case to case. In cases with chronic complications, it was inferred that there are different patterns in the kinetics of pDNA under ART, such as repeatedly increasing and decreasing greatly.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (44 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 13 results,  Open Access: 11 results,  Acknowledgement Compliant: 1 results) Presentation (30 results) (of which Int'l Joint Research: 7 results,  Invited: 1 results)

  • [Int'l Joint Research] ドルトムント工科大学(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Total HIV-1 DNA dynamics and influencing factors in long-term ART-treated Japanese adults: a retrospective longitudinal analysis.2018

    • Author(s)
      Stanoeva KR, König A, Fukuda A, Kawanami Y, Kuwata T, Satou Y, Matsushita S.
    • Journal Title

      J Acquir Immune Defic Syndr

      Volume: - Issue: 2 Pages: 239-247

    • DOI

      10.1097/qai.0000000000001662

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Osteoporosis-related fractures in HIV-infected patients receiving long-term tenofovir disoproxil fumarate: an observational cohort study2018

    • Author(s)
      Komatsu, A., Ikeda, A., Kikuchi, A., Minami, C., Tan, M., Matsushita, S.
    • Journal Title

      Drug Safety

      Volume: 印刷中 Issue: 9 Pages: 843-848

    • DOI

      10.1007/s40264-018-0665-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unique binding modes for the broad neutralizing activity of single-chain variable fragments (scFv) targeting CD4-induced epitopes2017

    • Author(s)
      T1.Tanaka, K., Kuwata, T., Alam, M., Kaplan., G, Takahama, S., Valdez, K.P.R., Roitburd-Berman, A., Gershoni. J.M., Matsushita, S.
    • Journal Title

      Retrovirology

      Volume: 14 Issue: 1 Pages: 44-59

    • DOI

      10.1186/s12977-017-0369-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Prevalence of High Antiretroviral Coverage and Viral Suppression in Japan: an Excellent Profile for a Downstream Human Immunodeficiency Virus Care Spectrum2017

    • Author(s)
      Miyazaki, N., Sugiura, W., Gatanaga, H., Watanabe, D., Yamamoto, Y., Yokomaku, Y., Yoshimura, K., Matsushita, S.
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 70 Issue: 2 Pages: 158-160

    • DOI

      10.7883/yoken.JJID.2015.599

    • NAID

      130005475411

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model2017

    • Author(s)
      Satou Yorifumi、Katsuya Hiroo、Fukuda Asami、Misawa Naoko、Ito Jumpei、Uchiyama Yoshikazu、Miyazato Paola、Islam Saiful、Fassati Ariberto、Melamed Anat、Bangham Charles R. M.、Koyanagi Yoshio、Sato Kei
    • Journal Title

      Scientific Reports

      Volume: 7(1) Issue: 1 Pages: 6913-6913

    • DOI

      10.1038/s41598-017-07307-4

    • NAID

      120006364095

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cross-Neutralization Activity of Single-Chain Variable Fragment (scFv) Derived from Anti-V3 Monoclonal Antibodies Mediated by Post-Attachment Binding2016

    • Author(s)
      Maruta, Y., Kuwata, T., Tanaka, K., Alam, M., Valdez, K. P., Egami, Y., Yoshiaki Suwa, Y., Morioka, H. and Matsushita, S.
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 69 Issue: 5 Pages: 395-404

    • DOI

      10.7883/yoken.JJID.2015.667

    • NAID

      130005416280

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors2016

    • Author(s)
      Alam, M., Kuwata, T., Shimura, K., Yokoyama, M., Ramirez Valdez, K. P., Tanaka, K., Maruta, Y., Oishi, S., Fujii, N., Sato, H., Matsuoka M. and Matsushita S.
    • Journal Title

      Retrovirology

      Volume: 13 Issue: 1 Pages: 70-70

    • DOI

      10.1186/s12977-016-0304-7

    • NAID

      120005973385

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of a neutralization-resistant CCR5 tropic SHIV-MK38 molecular clone, a derivative of SHIV-89.6.2016

    • Author(s)
      Ishida Yuki, Yoneda Mai, Otsuki Hiroyuki, Watanabe Yuji, Kato Fumihiro, Matuura Kanako, Kikukawa Minako, Matsushita Shuzo, Hishiki Takayuki, Igarashi Tatsuhiko, Miura Tomoyuki.
    • Journal Title

      J Gen Virol

      Volume: 97(5) Issue: 5 Pages: 1249-60

    • DOI

      10.1099/jgv.0.000421

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Small-Molecule CD4 Mimics Containing Mono-cyclohexyl Moieties as HIV Entry Inhibitors.2016

    • Author(s)
      Nami Ohashi1, Shigeyoshi Harada, Takaaki Mizuguchi1, Yu Irahara1, Yuko Yamada, Misato Kotani, Wataru Nomura, Shuzo Matsushita, Kazuhisa Yoshimura, Hirokazu Tamamura.
    • Journal Title

      Chem Med Chem

      Volume: 19 Issue: 8 Pages: 940-946

    • DOI

      10.1002/cmdc.201500590

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A minimally cytotoxic CD4 mimic as an HIV entry inhibitor2016

    • Author(s)
      Takaaki Mizuguchi, Shigeyoshi Harada, Tomoyuki Miura, Nami Ohashi, Tetsuo Narumi, Hiromi Mori, Yu Irahara, Yuko Yamada, Wataru Nomura, Shuzo Matsushita, Kazuhisa Yoshimura, Hirokazu Tamamura
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 26 Issue: 2 Pages: 397-400

    • DOI

      10.1016/j.bmcl.2015.11.103

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of the Maraviroc-Resistant Mutation M434I in the C4 Region of HIV-1 gp120 on Sensitivity to Antibody-Mediated Neutralization2016

    • Author(s)
      Samatchaya Boonchawalit, Shigeyoshi Harada, Noriko Shirai, Hiroyuki Gatanaga, Shinichi Oka, Shuzo Matsushita, Kazuhisa Yoshimura.
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 69 Issue: 3 Pages: 236-243

    • DOI

      10.7883/yoken.JJID.2015.310

    • NAID

      130005151997

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Incompatible Natures of the HIV-1 Envelope in Resistance to the CCR5 Antagonist Cenicriviroc and to Neutralizing Antibodies2016

    • Author(s)
      Kuwata T, Enomoto I, Baba M, Matsushita S
    • Journal Title

      Antimicrob Agents Chemother

      Volume: 60 Issue: 1 Pages: 437-450

    • DOI

      10.1128/aac.02285-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The retrovirus HTLV-1 inserts an ectopic CTCF-binding site into the human genome2016

    • Author(s)
      Satou Y, Miyazato P, Ishihara K, Yaguchi H, Melamed A, Miura M, Fukuda A, Nosaka K, Watanabe T, Rowan A, Nakao M, and Bangham CRM
    • Journal Title

      PNAS

      Volume: 113 Pages: 3054-3059

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Evaluation of HIV-1 Proviral DNA by Newly Established Approaches2018

    • Author(s)
      Islam Mohammad Saiful, Paola Miyazato, Kouki Matsuda, Benjy Tan Jek Yan, Saori Iwase, Yohei Seki, Kazuhisa Yoshimura, Hirofumi Akari, Kenji Maeda, Yorifumi Satou
    • Organizer
      JSPS_NUS Symposium
    • Related Report
      2017 Annual Research Report
  • [Presentation] Neutralization sensitivities of clade B and CRF01_AE viruses of HIV-1 isolated from patients with recent diagnosis in Japan.2017

    • Author(s)
      Thida, W., Kuwata T., Muntasir A., Tanaka K., Mamun M., Shimizu, M., Kawanami, Y., Matsushita S.
    • Organizer
      18th Kumamoto AIDS seminar
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evaluation of Binding affinity and kinetics, Neutralization Potency and Coverage of anti-V3 scFv’s against HIV-1 Subtype-B viruses in vitro.2017

    • Author(s)
      Mamun M., Maruta Y., Tanaka K., Muntasir A., Thida, W., Kuwata T., Matsushita S.
    • Organizer
      18th Kumamoto AIDS seminar.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Single cell sorting による抗 V3 中和 単クローン抗体に対する抗イディオタイプ.2017

    • Author(s)
      郭 悠, 桑田岳夫, 田中和樹, Alam Mohammad Mamun, 高濱正吉, Hassan MD Zahid, 松下修三.
    • Organizer
      第31回日本エイズ学会学術集会・総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Evaluation of Binding affinity and Neutralization Potency and coverage of anti-V3 scFv’sagainst HIV-1 subtype-B viruses.2017

    • Author(s)
      Alam Mohammad, 田中和樹, Muntasir Alam, Win Thida, 桑田岳夫, 松下修三.
    • Organizer
      第31回日本エイズ学会学術集会・総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Broadly neutralizing antibody for treatment and prevension of HIV infetion.2017

    • Author(s)
      Shuzo Matsushita
    • Organizer
      ISAAR & ICIC 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 次世代シークエンスによるヒト化マウスHIV-1感染モデルにおけるウイルス感染細胞クローン動態解析2017

    • Author(s)
      佐藤賢文、勝屋弘雄、福田麻美、三沢尚子、伊東潤平、内山良一、宮里パオラ、Mohammad S Islam、Ariberto Fassati、Charles RM Bangham、小柳義夫、佐藤圭
    • Organizer
      第27回抗ウイルス療法学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Improving the Resolution of HIV-1 Transcriptome Analysis Through Targeted Enrichment2017

    • Author(s)
      Benjy Tan Jek Yang, Miyazato Paola, Islam Mohammad Saiful, Iwase Saori, Kudo Eriko, Okada Seiji, Satou Yorifumi
    • Organizer
      第20回日本レトロウイルス研究会 夏期セミナー
    • Related Report
      2017 Annual Research Report
  • [Presentation] Absolute Quantitation of Integrated HIV-1 DNA In Vivo by using Droplet Digital PCR2017

    • Author(s)
      Islam Mohammad Saiful, Yohei Seki, Paola Miyazato, Benjy Tan Jek Yang, Hirofumi Akari and Yorifumi Satou
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Quantitative and Qualitative Evaluation of HIV-1 Proviral DNA by Droplet Digital PCR and High-throughput Sequencing2017

    • Author(s)
      Saiful Islam, Paola Miyazato, Yohei Seki, Benjy Tan Jek Yan, Saori Iwase, Hirofumi Akri, Yorifumi Satou
    • Organizer
      第18回熊本エイズ学セミナー
    • Related Report
      2017 Annual Research Report
  • [Presentation] High Resolution HIV-1 Provirus Transcriptome Analysis with DNA Probe Enrichment2017

    • Author(s)
      Benjy Tan Jek Yang, Miyazato Paola, Islam Mohammad Saiful, Iwase Saori, Kudo Eriko, Okada Seiji, Satou Yorifumi
    • Organizer
      第18回熊本エイズ学セミナー
    • Related Report
      2017 Annual Research Report
  • [Presentation] Quantitative and qualitative evaluation of HIV-1 proviral DNA by digital droplet PCR and high-throughput sequencing2017

    • Author(s)
      Islam Mohammad Saiful, Paola Miyazato, Yohei Seki, Benjy Tan Jek Yang, Saori Iwase, Hirofumi Akari, Yorifumi Satou
    • Organizer
      第31回日本エイズ学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] High Resolution HIV-1 Provirus Transcriptome Analysis with DNA Probe Enrichment2017

    • Author(s)
      Benjy Tan Jek Yang, Miyazato Paola, Islam Mohammad Saiful, Iwase Saori, Kudo Eriko, Okada Seiji, Satou Yorifumi
    • Organizer
      第31回日本エイズ学会学術集会・総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト細胞ゲノムDNAに組み込まれた外来性レトロウイルスの制御メカニズム2017

    • Author(s)
      佐藤賢文
    • Organizer
      第4回 関西ウイルスクラブ(KVC)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Incompatibility of HIV-1 Resistance to Both Cenicriviroc and Neutralizing Antibodies Boston, Massachusetts.2016

    • Author(s)
      Kuwata,T., Enomoto I., Baba M., Matsushita S.
    • Organizer
      Conference on Retroviruses and Opportunistic Infections
    • Place of Presentation
      Boston, USA
    • Year and Date
      2016-02-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] HIV proviral DNA quantification in a cohort of Japanese patients on longterm ART2016

    • Author(s)
      K. Stanoeva, A. Konig, A. Fukuda, Y. Kawanami, T. Kuwata, Y. Satou, S. Matsushita.
    • Organizer
      21st International AIDS Conference
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Increased total HIV DNA levels in long-term treated patients with hemophilia.2016

    • Author(s)
      Stanoeva K, Konig A, Fukuda A, Kawanami Y, Kuwata T, Satou Y., Matsushita S.
    • Organizer
      第30回日本エイズ学会学術集会・総会.
    • Related Report
      2016 Annual Research Report
  • [Presentation] Construction, purification and analysis of neutralization potency of anti-V3 scFv’s against HIV-1 strains in vitro.2016

    • Author(s)
      Mamun M., Maruta Y., Tanaka K., Muntasir A., Thida W., Kuwata T., Matsushita S.
    • Organizer
      2nd Kumamoto IRCMS International Symposium.17th Kumamoto AIDS seminar
    • Related Report
      2016 Annual Research Report
  • [Presentation] Isolation and characterization of HIV-1 envelope glycoprotein in Japanese patients with recent diagnosis.2016

    • Author(s)
      Thida W., Kuwata T., Muntasir A., Tanaka K., Mamun M., Shimuzu M., Kawanami Y., Matsushita S.
    • Organizer
      2nd Kumamoto IRCMS International Symposium.17th Kumamoto AIDS seminar
    • Related Report
      2016 Annual Research Report
  • [Presentation] Total HIV DNA levels dynamics upon ART initiation2016

    • Author(s)
      Stanoeva KR., Konig A., Fukuda A., Kawanami Y., Kuwata T., Satou Y., Matsushita S.
    • Organizer
      2nd Kumamoto IRCMS International Symposium.17th Kumamoto AIDS seminar
    • Related Report
      2016 Annual Research Report
  • [Presentation] Application of targeted enrichment to the next-generation sequencing of retroviruses integrated into the host human genome2016

    • Author(s)
      宮里パオラ
    • Organizer
      第64回 日本ウイルス学会学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Application of next generation sequencing to elucidate regulatory mechanism of retroviruses integrated into the host human genome2016

    • Author(s)
      佐藤賢文
    • Organizer
      第17回 熊本エイズセミナー
    • Related Report
      2016 Annual Research Report
  • [Presentation] Application of targeted enrichment to the next-generation sequencing of retroviruses integrated into the host human genome2016

    • Author(s)
      宮里パオラ
    • Organizer
      第17回 熊本エイズセミナー
    • Related Report
      2016 Annual Research Report
  • [Presentation] Quantification of HIV-1 proviral DNA in various tissues of a macaque model of HIV-1 infection2016

    • Author(s)
      Islam Mohammad Saiful
    • Organizer
      第17回 熊本エイズセミナー
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒトゲノムに組み込まれた外来性レトロウイルスの転写制御メカニズム2016

    • Author(s)
      佐藤賢文
    • Organizer
      大阪大学蛋白質研究所セミナー
    • Related Report
      2016 Annual Research Report
  • [Presentation] Towards HIV reservoir measurements in ART-treated patients: integrated DNA quantification and HIV-1 clone expansion in a Japanese cohort.2015

    • Author(s)
      Stanoeva, K, Fukuda, A, König A., Satou Y., Matsushita S.
    • Organizer
      37th International Workshop HIV Persistence during Therapy
    • Place of Presentation
      Miami, Florida, U.S.A.
    • Year and Date
      2015-12-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ファージ・ライブラリーを用いた抗 V3単クローン抗体のエピトープ解析.2015

    • Author(s)
      平田 泉、桑田岳夫、丸田泰広、田中和樹、Muntasir, A.、松下修三
    • Organizer
      第29回日本エイズ学会学術集会・総会
    • Place of Presentation
      東京ドームホテル、東京
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 軽度から中等度の腎機能障害があるHIV 1 感染症患者に E/C/F/TAF を投与した第 III 相臨床試験におけるアジア人での有効性及び安全性の評価.2015

    • Author(s)
      松下修三、中本泰充、池田篤史、Pozniak, A、Arribas, J、Gupta, S、Post, F、Fordyce, M.
    • Organizer
      第29回日本エイズ学会学術集会・総会
    • Place of Presentation
      東京ドームホテル、東京
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Effect of gp41 mutations on the sensitivity to neutralizing antibodies against HIV.2015

    • Author(s)
      Muntasir, A., Kuwata, T., Ramirez, K., Maruta, Y., Tanaka, K., Shimura, K., Oishi, S., Fujii, N., Matsuoka, M., Matsushita, S.
    • Organizer
      第29回日本エイズ学会学術集会・総会.
    • Place of Presentation
      東京ドームホテル、東京
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Potent and broad neutralizing activity of small antibody fragments targeting CD4i (CD4-induced) epitope.2015

    • Author(s)
      Tanaka, K., Kuwata, T., Maruta, Y., Ramirez, K., Alam, M., Egami, Ikumi Y., Enomoto, I., Kawanami, Y., Matsushita. S.
    • Organizer
      The 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015)
    • Place of Presentation
      Vancouver, Canada.
    • Year and Date
      2015-07-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2022-08-30  

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