ArticlePloS one2014
Ex vivo response to histone deacetylase (HDAC) inhibitors of the HIV long terminal repeat (LTR) derived from HIV-infected patients on antiretroviral therapy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Broad activation of latent HIV-1 in vivo.Nature communications · 2016Trial
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- Versatile HIV Rev-dependent reporter cell system for stringent and sensitive quantification of viral reservoirs, neutralizing antibodies, and restriction factors.Retrovirology · 2026Article
- Versatile HIV Rev-dependent reporter cell system for stringent and sensitive quantification of viral reservoirs, neutralizing antibodies, and restriction factors.bioRxiv : the preprint server for biology · 2025Article
- Genetic variation of the HIV-1 subtype C transmitted/founder viruses long terminal repeat elements and the impact on transcription activation potential and clinical disease outcomes.PLoS pathogens · 2023Article
- Changes to the Simian Immunodeficiency Virus (SIV) Reservoir and Enhanced SIV-Specific Responses in a Rhesus Macaque Model of Functional Cure after Serial Rounds of Romidepsin Administrations.Journal of virology · 2022Article
- So Pathogenic or So What?-A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research.Viruses · 2022Review
- Histone deacetylase inhibition reduces deleterious cytokine release induced by ingenol stimulation.Biochemical pharmacology · 2022Article
- Pharmacokinetics and Immunological Effects of Romidepsin in Rhesus Macaques.Frontiers in immunology · 2020Article
- Recovirus NS1-2 Has Viroporin Activity That Induces Aberrant Cellular Calcium Signaling To Facilitate Virus Replication.mSphere · 2019Article
- Impact of Myeloid Reservoirs in HIV Cure Trials.Current HIV/AIDS reports · 2019Review
- Regulation of Chemokines and Cytokines by Histone Deacetylases and an Update on Histone Decetylase Inhibitors in Human Diseases.International journal of molecular sciences · 2019Review
- HIV latency can be established in proliferating and nonproliferating resting CD4+ T cells in vitro: implications for latency reversal.AIDS (London, England) · 2019Article
- HIV latency reversing agents act through Tat post translational modifications.Retrovirology · 2018Article
- Strategies to target non-T-cell HIV reservoirs.Current opinion in HIV and AIDS · 2016Review
- Global strategies are required to cure and eliminate HBV infection.Nature reviews. Gastroenterology & hepatology · 2016Review
- Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal.EBioMedicine · 2016Article
- HIV-1 Latency and Eradication: Past, Present and Future.Current HIV research · 2016Review
- Impact of Chromatin on HIV Replication.Genes · 2015Review
- Epigenetic control of HIV-1 post integration latency: implications for therapy.Clinical epigenetics · 2015Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Histone deacetylase inhibitors (HDACi) can induce human immunodeficiency virus (HIV) transcription from the HIV long terminal repeat (LTR). However, ex vivo and in vivo responses to HDACi are variable and the activity of HDACi in cells other than T-cells have not been well characterised. Here, we developed a novel assay to determine the activity of HDACi on patient-derived HIV LTRs in different cell types. HIV LTRs from integrated virus were amplified using triple-nested Alu-PCR from total memory CD4+ T-cells (CD45RO+) isolated from HIV-infected patients prior to and following suppressive antiretroviral therapy. NL4-3 or patient-derived HIV LTRs were cloned into the chromatin forming episomal vector pCEP4, and the effect of HDACi investigated in the astrocyte and epithelial cell lines SVG and HeLa, respectively. There were no significant differences in the sequence of the HIV LTRs isolated from CD4+ T-cells prior to and after 18 months of combination antiretroviral therapy (cART). We found that in both cell lines, the HDACi panobinostat, trichostatin A, vorinostat and entinostat activated patient-derived HIV LTRs to similar levels seen with NL4-3 and all patient derived isolates had similar sensitivity to maximum HDACi stimulation. We observed a marked difference in the maximum fold induction of luciferase by HDACi in HeLa and SVG, suggesting that the effect of HDACi may be influenced by the cellular environment. Finally, we observed significant synergy in activation of the LTR with vorinostat and the viral protein Tat. Together, our results suggest that the LTR sequence of integrated virus is not a major determinant of a functional response to an HDACi.
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Registered trials
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.