ArticleJournal of virology2011
Transforming growth factor beta-induced reactivation of Epstein-Barr virus involves multiple Smad-binding elements cooperatively activating expression of the latent-lytic switch BZLF1 gene.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Laryngeal squamous cell carcinoma: a functional "two-hit" model of papillomavirus-Epstein-Barr virus synergistic carcinogenesis.Frontiers in cellular and infection microbiology · 2026Pooled it
- Systematic investigation reveals extensive Epstein-Barr virus transcriptional regulation of the human genome.Cell genomics · 2026Article
- Review
- Proteomic screening identifies HNRNPA2B1 as an epigenetic repressor of Epstein-Barr virus reactivation.Journal of virology · 2026Article
- Reconstructing EBV reactivation and DNA damage response kinetics in morphologic pseudotime.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Locus-specific proteomics identifies novel regulators of Epstein-Barr virus lytic reactivation.Journal of virology · 2026Article
- LMP2A regulates S901 phosphorylation of EphA2 to maintain EBV latent infection in gastric cancer.British journal of cancer · 2025Article
- Reconstructing EBV reactivation and DNA damage response kinetics in morphologic pseudotime.bioRxiv : the preprint server for biology · 2025Article
- Article
- A thorough insight into the life cycle of the Epstein-Barr virus. From the molecular to the organismal level.Current research in microbial sciences · 2025Review
- A distinct isoform of lymphoid enhancer binding factor 1 (LEF1) epigenetically restricts EBV reactivation to maintain viral latency.PLoS pathogens · 2023Article
- High-Risk Human Papillomavirus and Epstein-Barr Virus Coinfection: A Potential Role in Head and Neck Carcinogenesis.Biology · 2021Review
- Review
- Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.PLoS pathogens · 2021Article
- Signaling pathways of EBV-induced oncogenesis.Cancer cell international · 2021Review
- Innate Immune Modulation Induced by EBV Lytic Infection Promotes Endothelial Cell Inflammation and Vascular Injury in Scleroderma.Frontiers in immunology · 2021Observational
- Reactivation of Epstein-Barr Virus by HIF-1α Requires p53.Journal of virology · 2020Article
- MYC Controls the Epstein-Barr Virus Lytic Switch.Molecular cell · 2020Article
- Inhibition of Epstein-Barr Virus Replication in Human Papillomavirus-Immortalized Keratinocytes.Journal of virology · 2019Article
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Transforming growth factor β (TGF-β) physiologically induces Epstein-Barr virus (EBV) lytic infection by activating the expression of EBV's latent-lytic switch BZLF1 gene. Liang et al. (J. Biol. Chem. 277:23345-23357, 2002) previously identified a Smad-binding element (SBE) within the BZLF1 promoter, Zp; however, it accounts for only 20 to 30% of TGF-β-mediated activation of transcription from Zp. Here, we identified additional factors responsible for the rest of this activation. The incubation of EBV-positive MutuI cells with a TGF-β neutralizing antibody or inhibitors of the TGF-β type I receptor (TβRI) or Smad3 eliminated the TGF-β-induced reactivation of EBV. The coexpression of Smad2, Smad3, and Smad4 together with a constitutively active form of TβRI induced 15- to 25-fold transcription from Zp in gastric carcinoma AGS cells. By electrophoretic mobility shift assays, we identified four additional Smad-binding elements, named SBE2 to SBE5. Substitution mutations in individual SBEs reduced Smad-mediated activation of Zp by 20 to 60%; together, these mutations essentially eliminated it. Chromatin immunoprecipitation assays confirmed that Smad4 newly bound the Zp region of the EBV genome following the incubation of MutuI cells with TGF-β. SBE2 overlaps the ZEB-binding ZV silencing element of Zp. Depending upon posttranslational modifications, Smad4 either competed with ZEB1 for binding or formed a complex with ZEB1 on the Zp ZV element in a cell-free assay system. In transiently transfected cells, exogenously expressed ZEB1 inhibited Smad-mediated transcriptional activation from Zp. We conclude that TGF-β induces EBV lytic reactivation via the canonical Smad pathway by activating BZLF1 gene expression through multiple SBEs acting in concert.
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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.