ArticleAIDS (London, England)2015
Dose-responsive gene expression in suberoylanilide hydroxamic acid-treated resting CD4+ T cells.
Article in AIDS (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Review
- Cellular Gene Modulation of HIV-Infected CD4 T Cells in Response to Serial Treatment with the Histone Deacetylase Inhibitor Vorinostat.Journal of virology · 2020Article
- Targeted therapy for mTORC1-driven tumours through HDAC inhibition by exploiting innate vulnerability of mTORC1 hyper-activation.British journal of cancer · 2020Article
- Determinants of the efficacy of HIV latency-reversing agents and implications for drug and treatment design.JCI insight · 2018Article
- Glucose Can Epigenetically Alter the Gene Expression of Neurotrophic Factors in the Murine Brain Cells.Molecular neurobiology · 2018Article
- Transcriptional Modulation of Human Endogenous Retroviruses in Primary CD4+ T Cells Following Vorinostat Treatment.Frontiers in immunology · 2018Article
- Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency.The Journal of clinical investigation · 2017Article
- Genetic divergence in the transcriptional engram of chronic alcohol abuse: A laser-capture RNA-seq study of the mouse mesocorticolimbic system.Alcohol (Fayetteville, N.Y.) · 2017Article
- Potent and Targeted Activation of Latent HIV-1 Using the CRISPR/dCas9 Activator Complex.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- HIV-1 Latency and Eradication: Past, Present and Future.Current HIV research · 2016Review
- Mixed effects of suberoylanilide hydroxamic acid (SAHA) on the host transcriptome and proteome and their implications for HIV reactivation from latency.Antiviral research · 2015Article
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
designPersistent latently infected CD4 T cells represent a major obstacle to HIV eradication. Histone deacetylase inhibitors (HDACis) are a proposed activation therapy. However, off-target effects on gene expression in host immune cells are poorly understood. We hypothesized that HDACi-modulated genes would be best identified with a dose-response analysis.
methodsResting primary CD4 T cells were treated with 0.34, 1, 3, or 10 μmol/l of the HDACi, suberoylanilide hydroxamic acid (SAHA), for 24 h and subjected to microarray gene expression analysis. Genes with dose-correlated expression were filtered to identify a subset with consistent up or downregulation at each SAHA dose. Histone modifications were characterized in six SAHA dose-responsive genes by chromatin immunoprecipitation (ChIP-RT-qPCR).
resultsA large number of genes were shown to be upregulated (N = 657) or downregulated (N = 725) by SAHA in a dose-responsive manner (FDR-corrected P-value ≤ 0.5, fold change ≥|2|). Several genes (e.g. CINNAL1, DPEP2, H1F0, IRGM, PHF15, and SELL) are potential in-vivo biomarkers of SAHA activity. SAHA dose-responsive genes included transcription factors, HIV restriction factors, histone methyltransferases, and host proteins that interact with HIV. Pathway analysis suggested net downregulation of T-cell activation with increasing SAHA dose. Histone acetylation was not correlated with host gene expression, but plausible alternative mechanisms for SAHA-modulated gene expression were identified.
conclusionNumerous genes in CD4 T cells are modulated by SAHA in a dose-responsive manner, including genes that may negatively influence HIV activation from latency. Our study suggests that SAHA influences gene expression through a confluence of several mechanisms, including histone modification, and altered expression and activity of transcription factors.
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