Histone deacetylase inhibition reduces deleterious cytokine release induced by ingenol stimulation

Larragoite, Erin T.; Nell, Racheal A.; Martins, Laura J.; Barrows, Louis R.; Planelles, Vicente; Spivak, Adam M.

doi:10.1016/j.bcp.2021.114844

Cited by 3 publications

(2 citation statements)

References 58 publications

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“…Epigenetic LRAs target the chromatin restrictions that maintain HIV latency and include histone deacetylase inhibitors [21][22][23][24], histone methyltransferase inhibitors [25],…”

Section: Introductionmentioning

confidence: 99%

“…Epigenetic LRAs target the chromatin restrictions that maintain HIV latency and include histone deacetylase inhibitors [ 21 , 22 , 23 , 24 ], histone methyltransferase inhibitors [ 25 ], and bromo- and extra-terminal domain inhibitors [ 26 , 27 , 28 ]. Signal agonist LRAs stimulate immune signaling pathways in T cells, leading to transcriptional modifications and NF-κB activation.…”

Section: Introductionmentioning

confidence: 99%

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Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation

Zhu

Jiang

Liu

et al. 2023

IJMS

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Reversing HIV-1 latency promotes the killing of infected cells and is essential for cure strategies. However, current latency-reversing agents (LRAs) are not entirely effective and safe in activating latent viruses in patients. In this study, we investigated whether Scopoletin (6-Methoxy-7-hydroxycoumarin), an important coumarin phytoalexin found in plants with multiple pharmacological activities, can reactivate HIV-1 latency and elucidated its underlying mechanism. Using the Jurkat T cell model of HIV-1 latency, we found that Scopoletin can reactivate latent HIV-1 replication with a similar potency to Prostratin and did so in a dose- and time-dependent manner. Moreover, we provide evidence indicating that Scopoletin-induced HIV-1 reactivation involves the nuclear factor kappa B (NF-κB) signaling pathway. Importantly, Scopoletin did not have a stimulatory effect on T lymphocyte receptors or HIV-1 receptors. In conclusion, our study suggests that Scopoletin has the potential to reactivate latent HIV-1 without causing global T-cell activation, making it a promising treatment option for anti-HIV-1 latency strategies.

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“…Epigenetic LRAs target the chromatin restrictions that maintain HIV latency and include histone deacetylase inhibitors [21][22][23][24], histone methyltransferase inhibitors [25],…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation

Zhu

Jiang

Liu

et al. 2023

IJMS

View full text Add to dashboard Cite

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Impact of IL-15 and latency reversing agent combinations in the reactivation and NK cell-mediated suppression of the HIV reservoir

Covino

Desimio

Doria

2022

Sci Rep

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Inhibitors of histone deacetylases (HDACis) are major latency reversing agent (LRA) candidates in ‘shock and kill’ strategies to eradicate the HIV reservoir in infected patients. The poor achievements of initial HDACi-based trials and subsequent studies have highlighted the need for more efficient approaches such as combinatory and immunostimulating therapies. Here we studied combinations of IL-15 with pan-HDACi (Vorinostat, Romidepsin, Panobinostat) or class I selective-HDACi (Entinostat) with or without a PKC agonist (Prostratin) for their impact on in vitro reactivation and NK cell-mediated suppression of latent HIV. Results showed that pan-HDACis but not Entinostat reduced NK cell viability and function; yet, combined IL-15 reverted the negative effects of pan-HDACis except for Panobinostat. All HDACis were ineffective at reactivating HIV in a CD4+ T cell model of latency, with pan-HDACis suppressing spontaneous and IL-15- or Prostratin-induced HIV release, while IL-15 + Prostratin combination showed maximal activity. Moreover, Panobinostat impaired STAT5 and NF-κB activation by IL-15 and Prostratin, respectively. Finally, by using effectors (NK) and targets (latently infected CD4+ T cells) equally exposed to drug combinations, we found that IL-15-mediated suppression of HIV reactivation by NK cells was inhibited by Panobinostat. Our data raise concerns and encouragements for therapeutic application of IL-15/LRA combinations.

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Isoform-Selective Versus Nonselective Histone Deacetylase Inhibitors in HIV Latency Reversal

Boateng

Abaidoo-Myles

Bonney

et al. 2022

AIDS Research and Human Retroviruses

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Histone deacetylase inhibition reduces deleterious cytokine release induced by ingenol stimulation

Cited by 3 publications

References 58 publications

Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation

Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation

Impact of IL-15 and latency reversing agent combinations in the reactivation and NK cell-mediated suppression of the HIV reservoir

Isoform-Selective Versus Nonselective Histone Deacetylase Inhibitors in HIV Latency Reversal

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