Kagoshima University · Institute of Medical and Dental Sciences, Division of Human Retrovirology · 教授

Research keywordsAntiviral therapy・CMV・HBV・HIV-1・SARS-CoV-2

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• Yuichiro Hara, Haruki Kitamura, Kouki Matsuda, Sayaka Sukegawa, Kosuke Tanimoto, Chieko Fujisaki, Kenji Maeda, Hiroaki Takeuchi . Identification of a novel small molecule facilitating HIV elim2025 · 出版者・発行元： openRxiv Abstract The development of antiretroviral therapy (ART) has significantly improved the prognosis of people living with HIV (PLWH). However, reservoirs of latent viruses represent a major barrier to achieving a complete cure of HIV infection. To overcome the burden of viral latency, the “Shock-and-Kill” strategy employs latency-reversing agents (LRAs) to reactivate the virus and thus render it susceptible to elimination. Existing LRAs are not optimal and there is an unmet need for improvement. By screening a small molecule library, we identified the novel LRA candidate 2-HSB (2-hydrido-2,2’-spirobi(1,3,2-benzodioxaphosphole)) which not only reactivates latent HIV provirus but also induces specific cytopathic effects in both monocytic and T lymphocytic latent HIV reservoirs. Thus, this novel compound represents a dual “shock and kill” agent, unlike known LRAs which are limited to the “shock”. The probable involvement of HIV-1 tat protein may account for its selectivity. Although both shock and kill effects seemed to be regulated by spleen tyrosine kinase, they were independent of each other, indicating that neither activation-induced cell death nor cell death-induced reactivation was occurring. Crucially, 2-HSB induced viral transcription in ART-suppressed PLWH samples in vitro. Our findings present 2-HSB as a promising dual-action compound for the “Shock and Kill” strategy, demonstrating efficacy in both transformed cell lines and clinically-relevant primary samples. These results raise the possibility of distinguishing the mode of action of the two effects, potentially leading to the development of a single agent causing both HIV-1 reactivation and elimination and contributing to the improvement of treatment. DOI： 10.64898/2025.12.03.692014 researchmap
• Iwamoto N, Takamatsu Y, Asai Y, Tsuchiya K, Matsuda K, Oshiro Y, Inamura N, Terada M, Nemoto T, Kimura M, Saito S, Morioka S, Kenji M, Mitsuya H, Ohmagari N . High diagnostic accuracy o2024 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） DOI： 10.1016/j.heliyon.2024.e24513 PubMed researchmap
• Yamamoto S., Matsuda K., Maeda K., Horii K., Okudera K., Oshiro Y., Inamura N., Takeuchi J.S., Konishi M., Ozeki M., Mizoue T., Sugiyama H., Aoyanagi N., Mitsuya H., Sugiura W., Ohmagari N. .2023 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： International Journal of Infectious Diseases Objectives: To investigate the role of immunogenicity after the third vaccine dose against Omicron infection and COVID-19-compatible symptoms of infection. Methods: First, we examined vaccine effectiveness (VE) of the third dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of third vaccine recipients, we compared the preinfection live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls who had close contact with patients with COVID-19. Among these cases, we examined the association between NAb levels and the number of COVID-19-compatible symptoms. Results: Among the 1456 participants for VE analysis, 60 breakthrough infections occurred during the Omicron wave. The third dose VE for infection was 54.6%. Among the third dose recipients, NAb levels against Omicron did not differ between the cases (n = 22) and controls (n = 21). Among the cases, those who experienced COVID-19-compatible symptoms had lower NAb levels against Omicron than those who did not. Conclusion: The third vaccine dose was effective in decreasing the risk of SARS-CoV-2 infection during Omicron wave compared with the second dose. Among third dose recipients, higher preinfection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection. DOI： 10.1016/j.ijid.2023.01.023 Scopus PubMed researchmap
• Suzuki T, Asai Y, Takahashi K, Sanada M, Shimanishi Y, Terada M, Sato L, Inada M, Yamada G, Akiyama Y, Oshiro Y, Shiratori K, Togano T, Takamatsu Y, Kenji M, Matsunaga A, Ishizaka Y, Nomoto H, Iwamoto2023 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） DOI： 10.1016/j.heliyon.2023.e20568 PubMed researchmap

• 治療後も残存するHIVリザーバーの定量システム応用したエイズ治癒療法の開発2023 · 配分額： 4680000円 （ 直接経費： 3600000円 、 間接経費： 1080000円 ） 多剤併用療法（cART）の導入以降、HIV感染症治療は劇的に改善されたが、治癒に至る治療法はない。これはHIVリザーバーと呼ばれるHIV潜伏感染細胞がcART治療中も感染者体内に残存するためである。これに対して、HIV潜伏感染細胞活性化剤 （latency reversing agent: LRA）などを用いて潜伏感染細胞を活性化させた後に除去する治療法が提唱されているが、臨床で効果を発揮できるかはまだ不明である。このようなHIVリザーバーを標的とした治療法の確立には、HIV潜伏感染細胞の患者ごとの量的・質的評価を可能とする測定系の構築が必要となる。 本研究ではHIV潜伏感染（リザーバー）細胞の除去を可能とする新しい治療法の確立を目的とした研究を行って来た。まず治療中のHIV感染者の末梢血中に微量に残存するHIV潜伏感染細胞の量的・質的評価法の確立（Ex vivo reactivation法、およびデジタルPCRを用いたIPDA解析法）と生体でのダイナミクス解析、さらに体内のリザーバーサイズを反映するバイオマーカーの探索を進め、複数の因子が同定、RNA-seqを用いた解析も進めている。これらの多くは感染症、あるいは癌に関連すると報告されているものであるが、組み合わなどにより、HIV残存リザーバー量の指標、さらにはHIV潜伏感染細胞（リザーバー細胞）の活性化、不活化など、リザーバー治療の標的となるが可能性が考えられる。 このような成果により、HIV感染者の体内のリザーバーサイズの正確な予測を可能にすると共に、本研究で得られるHIV潜伏感染細胞を用いたEx Vivoでの薬効評価系も併用して新しいHIVリザーバー細胞治療薬の開発を目指す。 researchmap
• HIV残存ウイルスリザーバーの評価を可能とする新規バイオマーカー探索と治療法開発2020 · 担当区分： 研究代表者 researchmap
• COVID-19治療としての回復者血漿療法の基盤整備2020 · 担当区分： 研究代表者 researchmap
• 新型コロナウイルス感染症（COVID-19）の治療法を確立するための研究2020 · 担当区分： 研究分担者 researchmap

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