ArticleJCI insight2018
Histone H2A monoubiquitylation and p38-MAPKs regulate immediate-early gene-like reactivation of latent retrovirus HTLV-1.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 47 citations in OpenAlex.
- Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy.The Journal of clinical investigation · 2019Trial
- A multi-omics approach reveals specific oncogenic and inflammatory potential of viral oncoproteins Tax from neglected HTLV-1b and -1c genotypes.PLoS pathogens · 2026Article
- Intra-pol proviral open region of HTLV-1 controls the transcription from both long terminal repeats.Retrovirology · 2025Article
- Article
- The silence within: a conserved intragenic silencing element governs HTLV-1 expression via host RUNX1 complex binding.Npj viruses · 2025Article
- A statistical framework for quantifying the nuclear export rate of influenza viral mRNAs.eLife · 2025Article
- Sustained inflammation during human T-lymphotropic virus type 1 infection: a wildfire contributing to disease progression.Frontiers in medicine · 2025Review
- M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles.PLoS pathogens · 2025Article
- Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: A Comprehensive Review.Biomolecules · 2023Review
- The transcriptome of HTLV-1-infected primary cells following reactivation reveals changes to host gene expression central to the proviral life cycle.PLoS pathogens · 2023Article
- Article
- The Involvement of Ubiquitination and SUMOylation in Retroviruses Infection and Latency.Viruses · 2023Review
- Dynamics and consequences of the HTLV-1 proviral plus-strand burst.PLoS pathogens · 2022Article
- Review
- Time-course of host cell transcription during the HTLV-1 transcriptional burst.PLoS pathogens · 2022Article
- Current Perspectives in Human T-Cell Leukemia Virus Type 1 Infection and Its Associated Diseases.Frontiers in medicine · 2022Review
- HDAC inhibitors Panobinostat and Romidepsin enhanceFrontiers in immunology · 2022Article
- Reflections on Some of the Exceptional Features of HTLV-1 and HTLV-1 Research: A Perspective.Frontiers in immunology · 2022Article
- Epigenetic Regulation of Human T-Cell Leukemia Virus Gene Expression.Microorganisms · 2021Review
- M-Sec induced by HTLV-1 mediates an efficient viral transmission.PLoS pathogens · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
It is not understood how the human T cell leukemia virus human T-lymphotropic virus-1 (HTLV-1), a retrovirus, regulates the in vivo balance between transcriptional latency and reactivation. The HTLV-1 proviral plus-strand is typically transcriptionally silent in freshly isolated peripheral blood mononuclear cells from infected individuals, but after short-term ex vivo culture, there is a strong, spontaneous burst of proviral plus-strand transcription. Here, we demonstrate that proviral reactivation in freshly isolated, naturally infected primary CD4+ T cells has 3 key attributes characteristic of an immediate-early gene. Plus-strand transcription is p38-MAPK dependent and is not inhibited by protein synthesis inhibitors. Ubiquitylation of histone H2A (H2AK119ub1), a signature of polycomb repressive complex-1 (PRC1), is enriched at the latent HTLV-1 provirus, and immediate-early proviral reactivation is associated with rapid deubiquitylation of H2A at the provirus. Inhibition of deubiquitylation by the deubiquitinase (DUB) inhibitor PR619 reverses H2AK119ub1 depletion and strongly inhibits plus-strand transcription. We conclude that the HTLV-1 proviral plus-strand is regulated with characteristics of a cellular immediate-early gene, with a PRC1-dependent bivalent promoter sensitive to p38-MAPK signaling. Finally, we compare the epigenetic signatures of p38-MAPK inhibition, DUB inhibition, and glucose deprivation at the HTLV-1 provirus, and we show that these pathways act as independent checkpoints regulating proviral reactivation from latency.
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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.