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Analysis of multiple factors involved in the co-existence of R5 and X4 HIV-1s in the infected individuals

Research Project

Project/Area Number 19K08932
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Maeda Yosuke  熊本大学, 大学院生命科学研究部(医), 准教授 (30284764)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsHIV-1 / エイズ病態 / コレセプタースイッチ / コレセプター / CCR5 / CXCR4 / 混合感染 / coreceptor / AIDS
Outline of Research at the Start

HIV-1にはコレセプターとしてCCR5を使用して感染するR5ウイルスと,CXCR4を使用して感染するR5X4やX4ウイルスがある。一般には感染初期から後期にわたりR5ウイルスが持続感染しているが,感染後期にはCXCR4を利用するウイルスにスイッチするケースがあり,病態の悪化と関連している。本研究では同一個体からコレセプター利用性の異なる複数のウイルスを分離して,それぞれのウイルスがどのような機序で感染個体内で共存・維持されているかを明らかにする。このようなウイルスのスイッチの機序を解明することはHIV-1の感染免疫病態の理解,さらにはHIV-1治療・治癒に貢献することが期待される。

Outline of Final Research Achievements

HIV-1 is transmitted by CCR5-using HIV-1, and induces persistent infection. However, CXCR4-using X4 virus emerges in approximately half of HIV-1-infected individuals at late stage with higher viral load and disease progression called AIDS. However, it has been not fully understand how HIV-1 induces coreceptor switch from R5 to X4. In this study, we focused on subtype A/E in drug users (IDUs) in Vietnam, and found higher prevalence of X4 virus, and mixed infection with R5 virus. Nest generation analysis revealed that the frequency of mixed infection was much higher, indicating the role of mixed infection for the coreceptor switch from R5 to X4 at late stage. Interestingly, we further found that the viral load in mixed infection was significantly higher compared to that in homogenous infection. Take together, mixed infection of R5 and X4 may be involved in coreceptor switch and associated with higher viral load in late stage of infection.

Academic Significance and Societal Importance of the Research Achievements

HIV-1の中でR5ウイルスが基本的なウイルスに対して,X4ウイルスは感染後期のAIDSに観察されることが知られているが,このようなウイルスのスイッチがどのような機序でおこっているのかは明らかでなかった。今回の研究により,両者が同じ感染者に共存している場合,R5とX4ウイルスのどちらのウイルスが主要な集団となるかは,それぞれのウイルスの増殖できる生体内環境によることを明らかにした。したがって,今後の研究により,どのような生体内環境の変化がR5ウイルスからX4ウイルスへのスイッチにつながるのかが明らかとなれば,AIDSへの進行を防ぐHIV-1の新たな治療戦略につながることが期待される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (4 results) (of which Invited: 2 results)

  • [Int'l Joint Research] National Hospital of Tropical Medicine(ベトナム)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Plasma N‐Cleaved Galectin‐9 Is a Surrogate Marker for Determining the Severity of COVID‐19 and Monitoring the Therapeutic Effects of Tocilizumab2023

    • Author(s)
      Hozumi H, Maeda Y, Niki T, Chagan-Yasutan H, Bai G, Matsuba T, Furushima D, Ashino y, Hattori T
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 24 Issue: 4 Pages: 3591-3591

    • DOI

      10.3390/ijms24043591

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Control of HIV-1 Replication by CD8+ T Cells Specific for Two Novel Pol Protective Epitopes in HIV-1 Subtype A/E Infection.2022

    • Author(s)
      Nguyen HT, Kuse N, Zhang Y, Murakoshi H, Maeda Y, Tamura Y, Maruyama R, Tran GV, Nguyen TV, Nguyen KV, Oka S, Chikata T, Takiguchi M.
    • Journal Title

      Journal of Virology

      Volume: 96 Issue: 19

    • DOI

      10.1128/jvi.00811-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Resistance of SARS-CoV-2 variants to neutralization by antibodies induced in convalescent patients with COVID-192021

    • Author(s)
      Kaku Y, Kuwata T, Zahid HM, Hashiguchi T, Noda T, Kuramoto N, Biswas S, Matsumoto K, Shimizu M, Kawanami Y, Shimura K, Onishi C, Muramoto Y, Suzuki T, Sasaki J, Nagasaki Y, Minami R, Motozono C, Toyoda M, Takahashi H, Kishi H, Fujii K, Tatsuke T, Ikeda T, Maeda Y, Ueno T, Koyanagi Y, Iwagoe H, Matsushita S.
    • Journal Title

      Cell Reports

      Volume: 36 Issue: 2 Pages: 109385-109385

    • DOI

      10.1016/j.celrep.2021.109385

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia2021

    • Author(s)
      Bai Gaowa、Furushima Daisuke、Niki Toshiro、Matsuba Takashi、Maeda Yosuke、Takahashi Atsushi、Hattori Toshio、Ashino Yugo
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 9 Pages: 4978-4978

    • DOI

      10.3390/ijms22094978

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High levels of the cleaved form of galectin-9 and osteopontin in the plasma are associated with inflammatory markers that reflect the severity of COVID-19 pneumonia2021

    • Author(s)
      Bai G, Furushima D, Niki T, Matsuba T, Maeda Y, Takahashi A, Hattori T, Ashino Y
    • Journal Title

      Int J Mol Sci in press

      Volume: in press

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Existence of replication-competent minor variants with different coreceptor usage in plasma from HIV-1-infected individuals2020

    • Author(s)
      Maeda Y, Takemura T, Chikata T, Kuwata T, Terasawa H, Fujimoto R, Kuse N, Akahoshi T, Murakoshi H, Van Tran G, Zhang Y, Pham CH, Pham AHQ, Monde K, Sawa T, Matsushita S, Nguyen TV, Van Nguyen K, Hasebe F, Yamashiro T, Takiguchi M.
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 12

    • DOI

      10.1128/jvi.00193-20

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Plasma Levels of a Cleaved Form of Galectin-9 Are the Most Sensitive Biomarkers of Acquired Immune Deficiency Syndrome and Tuberculosis Coinfection2020

    • Author(s)
      Padilla ST, Niki T, Furushima D, Bai G, Chagan-Yasutan H, Telan EF, Tactacan-Abrenica RJ, Maeda Y, Solante R, Hattori T
    • Journal Title

      Biomolecules

      Volume: 10 Issue: 11 Pages: 1495-1495

    • DOI

      10.3390/biom10111495

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Phosphatidylinositol 3-Kinase p110α/PTEN Signaling Pathway Is Crucial for HIV-1 Entry2019

    • Author(s)
      Hamada K, Maeda Y, Mizutani A, Okada S
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 1 Pages: 130-138

    • DOI

      10.1248/bpb.b18-00801

    • NAID

      130007542232

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-01-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of conventional antibodies targeting the CD4 binding site and CD4-induced epitopes in the control of HIV-1 CRF01_AE viruses.2019

    • Author(s)
      Thida W, Kuwata T, Maeda Y, Yamashiro T, Tran GV, Nguyen KV, Takiguchi M, Gatanaga H, Tanaka K, Matsushita S
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 508 Issue: 1 Pages: 46-51

    • DOI

      10.1016/j.bbrc.2018.11.063

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 天然化合物ライブラリーによる HIV-1放出阻害剤の探索2022

    • Author(s)
      田原 由莉歌、戸上 暉大、立石 大、門出 奈美、寺 沢 広美、澤 智裕、前田 洋助、渡邊 高志、藤田 美歌子、門出 和精
    • Organizer
      第69回日本ウイルス学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] High frequency of mixed infection with different coreceptor usage in CRF01_AE-HIV-1-infected intravenous drug users2021

    • Author(s)
      Yosuke Maeda, Takayuki Chikata, Taichiro Takemura, Hiromi Terasawa, Matsufuji Tetsu, Nozomi Kuse, Kazuaki Monde, Tomohiro Sawa, Futoshi Hasebe, Masafumi Takiguchi
    • Organizer
      第68回日本ウイルス学会学術集会・総会
    • Related Report
      2021 Research-status Report
  • [Presentation] The existence of replication-competent minor variants with different coreceptor usage in CRF01_AE HIV-1-infected individuals in northern Vietnam2019

    • Author(s)
      前田 洋助
    • Organizer
      日本学術振興会研究拠点形成事業シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ウイルスから見たHIV/AIDS2019

    • Author(s)
      前田 洋助
    • Organizer
      災害・熱帯感染症国際セミナー
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2024-01-30  

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