4-phenylquinoline-8-amine induces HIV-1 reactivation and apoptosis in latently HIV-1 infected cells.
In: Biochemical and biophysical research communications, Jg. 641 (2023-01-22), S. 139-147
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Zugriff:
Combinational antiretroviral therapy (cART) dramatically suppresses the viral load to undetectable levels in human immunodeficiency virus (HIV)-infected patients. However, HIV-1 reservoirs in CD4+T cells and myeloid cells, which can evade cART and host antiviral immune systems, are still significant obstacles to HIV-1 eradication. The "Shock and Kill" approach using latently-reversing agents (LRAs) is therefore currently developing strategies for effective HIV-1 reactivation from latency and inducing cell death. Here, we performed small-molecular chemical library screening with monocytic HIV-1 latently-infected model cells, THP-1 Nluc #225, and identified 4-phenylquinoline-8-amine (PQA) as a novel LRA candidate. PQA induced efficient HIV-1 reactivation in combination with PKC agonists including Prostratin and showed a similar tendency for HIV-1 activation in primary HIV-1 reservoirs. Furthermore, PQA induced killing of HIV-1 latently-infected cells. RNA-sequencing analysis revealed PQA had different functional mechanisms from PKC agonists, and oxidative stress-inducible genes including DDIT3 or CTSD were only involved in PQA-mediated cell death. In summary, PQA is a potential LRA lead compound that exerts novel functions related to HIV-1 activation and apoptosis-mediated cell death to eliminate HIV-1 reservoirs.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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4-phenylquinoline-8-amine induces HIV-1 reactivation and apoptosis in latently HIV-1 infected cells.
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Autor/in / Beteiligte Person: | Kitamura, H ; Sukegawa, S ; Matsuda, K ; Tanimoto, K ; Kobayakawa, T ; Takahashi, K ; Tamamura, H ; Tsuchiya, K ; Gatanaga, H ; Maeda, K ; Takeuchi, H |
Zeitschrift: | Biochemical and biophysical research communications, Jg. 641 (2023-01-22), S. 139-147 |
Veröffentlichung: | <2002- >: San Diego, CA : Elsevier ; <i>Original Publication</i>: New York, Academic Press., 2023 |
Medientyp: | academicJournal |
ISSN: | 1090-2104 (electronic) |
DOI: | 10.1016/j.bbrc.2022.12.024 |
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