ArticleProceedings of the National Academy of Sciences of the United States of America2018
Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
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Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 187 citations in OpenAlex.
- Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Guideline
- Review
- HTLV-1 Tax and HBZ cooperatively promote leukemogenesis through miR-155-mediated PTEN suppression and PI3K-Akt activation.Journal of virology · 2026Article
- The mJournal of virology · 2026Article
- HTLV-1 Tax Reshapes the DNA-Binding Pattern of Transcription Factor IRF4 and Disrupts Host Gene Regulation.Cancer science · 2026Article
- Transferrin Receptor Marks a Foxp3-Low Treg-like Inflammatory T Cell Subset Associated with Disease Severity in HAM/TSP.Pathogens (Basel, Switzerland) · 2026Article
- Viral-driven oncogenesis in T/NK-cell lymphomas: parallels and divergences between HTLV-1 and EBV.International journal of hematology · 2026Review
- Article
- Review
- Adult T-cell leukemia/lymphoma: molecular pathogenesis, emerging therapies, and future directions.Frontiers in oncology · 2026Review
- Intra-pol proviral open region of HTLV-1 controls the transcription from both long terminal repeats.Retrovirology · 2025Article
- Article
- Viral oncogenes drive biphenotypic lymphoproliferative malignancy in transgenic mice.Scientific reports · 2025Article
- Review
- An HTLV-1-Infected Humanized Mouse Model Expressing HLA-A*02:01 Demonstrates Effective CTL-Mediated Suppression of HTLV-1.Viruses · 2025Article
- Splicing-dependent restriction of the HBZ gene by Tax underlies biphasic HTLV-1 infection.PLoS pathogens · 2025Article
- JunB-HBZ nuclear translocation by TGF-β is a key driver in HTLV-1-mediated leukemogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Role of the CTCF binding site in Human T-Cell Leukemia Virus-1 pathogenesis.PLoS pathogens · 2025Article
- Intragenic viral silencer element regulates HTLV-1 latency via RUNX complex recruitment.Nature microbiology · 2025Article
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025Review
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viruses causing chronic infection artfully manipulate infected cells to enable viral persistence in vivo under the pressure of immunity. Human T-cell leukemia virus type 1 (HTLV-1) establishes persistent infection mainly in CD4+ T cells in vivo and induces leukemia in this subset. HTLV-1-encoded Tax is a critical transactivator of viral replication and a potent oncoprotein, but its significance in pathogenesis remains obscure due to its very low level of expression in vivo. Here, we show that Tax is expressed in a minor fraction of leukemic cells at any given time, and importantly, its expression spontaneously switches between on and off states. Live cell imaging revealed that the average duration of one episode of Tax expression is ∼19 hours. Knockdown of Tax rapidly induced apoptosis in most cells, indicating that Tax is critical for maintaining the population, even if its short-term expression is limited to a small subpopulation. Single-cell analysis and computational simulation suggest that transient Tax expression triggers antiapoptotic machinery, and this effect continues even after Tax expression is diminished; this activation of the antiapoptotic machinery is the critical event for maintaining the population. In addition, Tax is induced by various cytotoxic stresses and also promotes HTLV-1 replication. Thus, it seems that Tax protects infected cells from apoptosis and increases the chance of viral transmission at a critical moment. Keeping the expression of Tax minimal but inducible on demand is, therefore, a fundamental strategy of HTLV-1 to promote persistent infection and leukemogenesis.
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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.