ArticleAntiviral research2015
Mixed effects of suberoylanilide hydroxamic acid (SAHA) on the host transcriptome and proteome and their implications for HIV reactivation from latency.
Article in Antiviral research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 33 citations in OpenAlex.
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- Adeno-Associated Virus (AAV)-Delivered Exosomal TAT and BiTE Molecule CD4-αCD3 Facilitate the Elimination of CD4 T Cells Harboring Latent HIV-1.Microorganisms · 2024Article
- Single-cell RNA sequencing reveals common and unique gene expression profiles in primary CD4+ T cells latently infected with HIV under different conditions.Frontiers in cellular and infection microbiology · 2023Article
- Integrated proteomics and transcriptomics analyses identify novel cell surface markers of HIV latency.Virology · 2022Article
- Are BET Inhibitors yet Promising Latency-Reversing Agents for HIV-1 Reactivation in AIDS Therapy?Viruses · 2021Review
- Micro RNA Targets in HIV Latency: Insights into Novel Layers of Latency Control.AIDS research and human retroviruses · 2021Article
- HIV and Proteomics: What We Have Learned from High Throughput Studies.Proteomics. Clinical applications · 2021Review
- 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
- Use of GapmeRs for gene expression knockdowns in human primary resting CD4+ T cells.Journal of immunological methods · 2020Article
- Histone deacetylase inhibitors induce complex host responses that contribute to differential potencies of these compounds in HIV reactivation.The Journal of biological chemistry · 2019Article
- Long non-coding RNAs and latent HIV - A search for novel targets for latency reversal.PloS one · 2019Article
- Epigenetic modulator UVI5008 inhibits MRSA by interfering with bacterial gyrase.Scientific reports · 2018Article
- Identification of Potential Therapeutic Targets in the Liver of Pioglitazone-Treated Type 2 Diabetes Sprague-Dawley Rats via Expression Profile Chip and iTRAQ Assay.Journal of diabetes research · 2018Article
- Transcriptional Modulation of Human Endogenous Retroviruses in Primary CD4+ T Cells Following Vorinostat Treatment.Frontiers in immunology · 2018Article
- Systems proteomic analysis reveals that clusterin and tissue inhibitor of metalloproteinases 3 increase in leptomeningeal arteries affected by cerebral amyloid angiopathy.Neuropathology and applied neurobiology · 2017Article
- Structure-optimized dihydropyranoindole derivative GIBH-LRA002 potentially reactivated viral latency in primary CD4+ T lymphocytes of chronic HIV-1 patients.MedChemComm · 2017Article
- Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency.The Journal of clinical investigation · 2017Article
- Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques.AIDS (London, England) · 2017Article
- Transcriptomic Analysis Implicates the p53 Signaling Pathway in the Establishment of HIV-1 Latency in Central Memory CD4 T Cells in an In Vitro Model.PLoS pathogens · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Suberoylanilide hydroxamic acid (SAHA) has been assessed in clinical trials as part of a "shock and kill" strategy to cure HIV-infected patients. While it was effective at inducing expression of HIV RNA ("shock"), treatment with SAHA did not result in a reduction of reservoir size ("kill"). We therefore utilized a combined analysis of effects of SAHA on the host transcriptome and proteome to dissect its mechanisms of action that may explain its limited success in "shock and kill" strategies. CD4+ T cells from HIV seronegative donors were treated with 1μM SAHA or its solvent dimethyl sulfoxide (DMSO) for 24h. Protein expression and post-translational modifications were measured with iTRAQ proteomics using ultra high-precision two-dimensional liquid chromatography-tandem mass spectrometry. Gene expression was assessed by Illumina microarrays. Using limma package in the R computing environment, we identified 185 proteins, 18 phosphorylated forms, 4 acetylated forms and 2982 genes, whose expression was modulated by SAHA. A protein interaction network integrating these 4 data types identified the HIV transcriptional repressor HMGA1 to be upregulated by SAHA at the transcript, protein and acetylated protein levels. Further functional category assessment of proteins and genes modulated by SAHA identified gene ontology terms related to NFκB signaling, protein folding and autophagy, which are all relevant to HIV reactivation. In summary, SAHA modulated numerous host cell transcripts, proteins and post-translational modifications of proteins, which would be expected to have very mixed effects on the induction of HIV-specific transcription and protein function. Proteome profiling highlighted a number of potential counter-regulatory effects of SAHA with respect to viral induction, which transcriptome profiling alone would not have identified. These observations could lead to a more informed selection and design of other HDACi with a more refined targeting profile, and prioritization of latency reversing agents of other classes to be used in combination with SAHA to achieve more potent induction of HIV expression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.