ArticleProceedings of the National Academy of Sciences of the United States of America2005
Valproate activates bovine leukemia virus gene expression, triggers apoptosis, and induces leukemia/lymphoma regression in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
- Exhausted CD4Frontiers in immunology · 2026Article
- The Complexity of Bovine Leukemia Virus Oncogenesis.Viruses · 2025Review
- Valproic Acid Enhances Venetoclax Efficacy in Targeting Acute Myeloid Leukemia.Diseases (Basel, Switzerland) · 2025Article
- Reduction of antisense transcription affects bovine leukemia virus replication and oncogenesis.PLoS pathogens · 2024Article
- Review
- A complex network of transcription factors and epigenetic regulators involved in bovine leukemia virus transcriptional regulation.Retrovirology · 2023Review
- Article
- The contribution of bovines to human health against viral infections.Environmental science and pollution research international · 2021Review
- Latency Reversing Agents: Kick and Kill of HTLV-1?International journal of molecular sciences · 2021Review
- Short-term cultured autologous peripheral blood mononuclear cells as a potential immunogen to activate Tax-specific CTL response in adult T-cell leukemia patients.Cancer science · 2021Article
- Effects of Naturally Occurring Mutations in Bovine Leukemia Virus 5'-LTR and Tax Gene on Viral Transcriptional Activity.Pathogens (Basel, Switzerland) · 2020Article
- Regulation of Expression and Latency in BLV and HTLV.Viruses · 2020Review
- Article
- Ablation of non-coding RNAs affects bovine leukemia virus B lymphocyte proliferation and abrogates oncogenesis.PLoS pathogens · 2020Article
- BLV: lessons on vaccine development.Retrovirology · 2019Review
- How Does HTLV-1 Undergo Oncogene-Dependent Replication Despite a Strong Immune Response?Frontiers in microbiology · 2017Article
- Recent Advances in BLV Research.Viruses · 2015Review
- Valproic acid improves second-line regimen of small cell lung carcinoma in preclinical models.ERJ open research · 2015Article
- Characteristics of Adult T-Cell Leukemia/Lymphoma Patients with Long Survival: Prognostic Significance of Skin Lesions and Possible Beneficial Role of Valproic Acid.Leukemia research and treatment · 2015Article
- Valproic acid suppresses Nrf2/Keap1 dependent antioxidant protection through induction of endoplasmic reticulum stress and Keap1 promoter DNA demethylation in human lens epithelial cells.Experimental eye research · 2014Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukemogenic viruses like human T-lymphotropic virus and bovine leukemia virus (BLV) presumably persist in the host partly by latent integration of the provirus in a fraction of infected cells, leading to accumulative increase in the outgrowth of transformed cells. Furthermore, viral infection also correlates with a blockade of the apoptotic mechanisms concomitant with an apparent latency of the host cell. Conceptually, induction of viral or cellular gene expression could thus also be used as a therapeutic strategy against retroviral-associated leukemia. Here, we provide evidence that valproate, an inhibitor of deacetylases, activates BLV gene expression in transient transfection experiments and in short-term cultures of primary B-lymphocytes. In vivo, valproate injection into newly BLV-inoculated sheep did not abrogate primary infection. However, valproate treatment, in the absence of any other cytotoxic drug, was efficient for leukemia/lymphoma therapy in the sheep model leading to decreased lymphocyte numbers (respectively from 25.6, 35.7, and 46.5 x 10(3) cells per mm3 to 1.0, 10.6, and 24.3 x 10(3) cells per mm3 in three leukemic sheep) and tumor regression (from >700 cm3 to undetectable). The concept of a therapy that targets the expression of viral and cellular genes might be a promising treatment of adult T cell leukemia or tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy, diseases for which no satisfactory treatment exists so far.
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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.