Histone deacetylase inhibitor Scriptaid reactivates latent HIV-1 promoter by inducing histone modification in in vitro latency cell lines

  • Authors:
    • Hao Ying
    • Yuhao Zhang
    • Shiguan Lin
    • Yefei Han
    • Huan-Zhang Zhu
  • View Affiliations

  • Published online on: August 1, 2010     https://doi.org/10.3892/ijmm_00000461
  • Pages: 265-272
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Abstract

Human immunodeficiency virus type 1 (HIV-1) latency remains a major problem for the eradication of viruses in infected individuals undergoing highly active anti-retroviral therapy. By inhibiting HIV-1 gene expression and virus production, histone deacetylase (HDAC) may contribute to the quiescence of HIV-1 within resting CD4+ T cells. A novel HDAC inhibitor, Scriptaid, has been found to have robust activity and lower toxicity compared to trichostatin A (TSA). We therefore investigated Scriptaid for its capability to reverse HIV-1 latency by inducing HIV-1 activation in the Jurkat T cell line containing latent HIV proviruses. We found that Scriptaid can activate HIV-1 gene expression in these latent infected cells by 2-15-fold over background levels, as analyzed by flow cytometry. Chromatin immunoprecipitation (ChIP) assays further revealed that the Scriptaid increased the acetylation level of histones H3 and H4 at the nucleosome 1 site of the HIV-1 long terminal repeat compared to mock treatment. In addition, Scriptaid can synergize with prostratin or tumor necrosis factor-α to activate the HIV-1 promoter, with relatively lower toxicity compared to TSA. These studies suggest the potential of Scriptaid in anti-latency therapies.

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August 2010
Volume 26 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Ying, H., Zhang, Y., Lin, S., Han, Y., & Zhu, H. (2010). Histone deacetylase inhibitor Scriptaid reactivates latent HIV-1 promoter by inducing histone modification in in vitro latency cell lines. International Journal of Molecular Medicine, 26, 265-272. https://doi.org/10.3892/ijmm_00000461
MLA
Ying, H., Zhang, Y., Lin, S., Han, Y., Zhu, H."Histone deacetylase inhibitor Scriptaid reactivates latent HIV-1 promoter by inducing histone modification in in vitro latency cell lines". International Journal of Molecular Medicine 26.2 (2010): 265-272.
Chicago
Ying, H., Zhang, Y., Lin, S., Han, Y., Zhu, H."Histone deacetylase inhibitor Scriptaid reactivates latent HIV-1 promoter by inducing histone modification in in vitro latency cell lines". International Journal of Molecular Medicine 26, no. 2 (2010): 265-272. https://doi.org/10.3892/ijmm_00000461