Arsenic Trioxide Impacts Viral Latency and Delays Viral Rebound after Termination of ART in Chronically SIV‐Infected Macaques
Abstract: The latent viral reservoir is the source of viral rebound after interruption of antiretroviral therapy (ART) and is the major obstacle in eradicating the latent human immunodeficiency virus‐1 (HIV‐1). In this study, arsenic class of mineral, arsenic trioxide, clinically approved for treating acute promyelocytic leukemia, is demonstrated to reactivate latent provirus in CD4+ T cells from HIV‐1 patients and Simian immunodeficiency virus (SIV)‐infected macaques, without significant systemic T cell activation and inflammatory responses. In a proof‐of‐concept study using chronically SIVmac239‐infected macaques, arsenic trioxide combined with ART delays viral rebound after ART termination, reduces the integrated SIV DNA copies in CD4+ T cells, and restores CD4+ T cells counts in vivo. Most importantly, half of arsenic trioxide‐treated macaques show no detectable viral rebound in the plasma for at least 80 days after ART discontinuation. Mechanistically, the study reveals that CD4 receptors and CCR5 co‐receptors of CD4+ T cells are significantly downregulated by arsenic trioxide treatment, which reduces susceptibility to infection after provirus reactivation. Furthermore, an increase in SIV‐specific immune responses after arsenic trioxide treatment may contribute to suppression of viral rebound. This work suggests that arsenic trioxide in combination with ART is a novel regimen in down‐sizing or even eradicating latent HIV‐1 reservoir.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Arsenic Trioxide Impacts Viral Latency and Delays Viral Rebound after Termination of ART in Chronically SIV‐Infected Macaques ; volume:6 ; number:13 ; year:2019 ; extent:10
Advanced science ; 6, Heft 13 (2019) (gesamt 10)
- Urheber
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Yang, Qing
Feng, Fengling
Li, Pingchao
Pan, Enxiang
Wu, Chunxiu
He, Yizi
Zhang, Fan
Zhao, Jin
Li, Ruiting
Feng, Liqiang
Hu, Fengyu
Li, Linghua
Zou, Huachun
Cai, Weiping
Lehner, Thomas
Sun, Caijun
Chen, Ling
- DOI
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10.1002/advs.201900319
- URN
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urn:nbn:de:101:1-2022073111564410121115
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
- 15.08.2025, 05:29 UTC
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Yang, Qing
- Feng, Fengling
- Li, Pingchao
- Pan, Enxiang
- Wu, Chunxiu
- He, Yizi
- Zhang, Fan
- Zhao, Jin
- Li, Ruiting
- Feng, Liqiang
- Hu, Fengyu
- Li, Linghua
- Zou, Huachun
- Cai, Weiping
- Lehner, Thomas
- Sun, Caijun
- Chen, Ling
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