ArticleJournal of virology2010
Phorbol ester-induced human cytomegalovirus major immediate-early (MIE) enhancer activation through PKC-delta, CREB, and NF-kappaB desilences MIE gene expression in quiescently infected human pluripotent NTera2 cells.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Positive selection screen identifies natural product β-catenin inactivators.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Reactivation and Management of Endogenous Latent Herpesviruses in the Spaceflight Environment.Current microbiology · 2026Review
- Host-virus resilience networks and viral inflammaging circuits in aging and long COVID: a CMV-centered perspective.Frontiers in cellular and infection microbiology · 2026Review
- Cell type differences in human cytomegalovirus transcription and epigenetic regulation with insights into major immediate-early enhancer-promoter control.PLoS pathogens · 2025Article
- NFκB and Cyclic AMP Response Element Sites Mediate the Valproic Acid and UL138 Responsiveness of the Human Cytomegalovirus Major Immediate Early Enhancer and Promoter.Journal of virology · 2023Article
- A Tale of Usurpation and Subversion: SUMO-Dependent Integrity of Promyelocytic Leukemia Nuclear Bodies at the Crossroad of Infection and Immunity.Frontiers in cell and developmental biology · 2021Review
- FOXO transcription factors activate alternative major immediate early promoters to induce human cytomegalovirus reactivation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Human cytomegalovirus major immediate early transcripts arise predominantly from the canonical major immediate early promoter in reactivating progenitor-derived dendritic cells.The Journal of general virology · 2020Article
- Cytomegalovirus Latency and Reactivation: An Intricate Interplay With the Host Immune Response.Frontiers in cellular and infection microbiology · 2020Review
- Control of Immediate Early Gene Expression for Human Cytomegalovirus Reactivation.Frontiers in cellular and infection microbiology · 2020Review
- Expanding the Known Functional Repertoire of the Human Cytomegalovirus pp71 Protein.Frontiers in cellular and infection microbiology · 2020Review
- Alternative promoters drive human cytomegalovirus reactivation from latency.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Chromatin Profiles of Chromosomally Integrated Human Herpesvirus-6A.Frontiers in microbiology · 2019Article
- Molecular Determinants and the Regulation of Human Cytomegalovirus Latency and Reactivation.Viruses · 2018Review
- Regulation ofPhysiological reports · 2017Article
- Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency.Virology · 2017Article
- Differentiation-Coupled Induction of Human Cytomegalovirus Replication by Union of the Major Enhancer Retinoic Acid, Cyclic AMP, and NF-κB Response Elements.Journal of virology · 2015Article
- Article
- The human cytomegalovirus UL133-138 gene locus attenuates the lytic viral cycle in fibroblasts.PloS one · 2015Article
- Mitogen and stress activated kinases act co-operatively with CREB during the induction of human cytomegalovirus immediate-early gene expression from latency.PLoS pathogens · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The ways in which human cytomegalovirus (HCMV) major immediate-early (MIE) gene expression breaks silence from latency to initiate the viral replicative cycle are poorly understood. A delineation of the signaling cascades that desilence the HCMV MIE genes during viral quiescence in the human pluripotent N-Tera2 (NT2) cell model provides insight into the molecular mechanisms underlying HCMV reactivation. In this model, we show that phorbol 12-myristate 13-acetate (PMA) immediately activates the expression of HCMV MIE RNA and protein and greatly increases the MIE-positive (MIE(+)) NT2 cell population density; levels of Oct4 (pluripotent cell marker) and HCMV genome penetration are unchanged. Decreasing PKC-delta activity (pharmacological, dominant-negative, or RNA interference [RNAi] method) attenuates PMA-activated MIE gene expression. MIE gene activation coincides with PKC-delta Thr505 phosphorylation. Mutations in MIE enhancer binding sites for either CREB (cyclic AMP [cAMP] response element [CRE]) or NF-kappaB (kappaB) partially block PMA-activated MIE gene expression; the ETS binding site is negligibly involved, and kappaB does not confer MIE gene activation by vasoactive intestinal peptide (VIP). The PMA response is also partially attenuated by the RNAi-mediated depletion of the CREB or NF-kappaB subunit RelA or p50; it is not diminished by TORC2 knockdown or accompanied by TORC2 dephosphorylation. Mutations in both CRE and kappaB fully abolish PMA-activated MIE gene expression. Thus, PMA stimulates a PKC-delta-dependent, TORC2-independent signaling cascade that acts through cellular CREB and NF-kappaB, as well as their cognate binding sites in the MIE enhancer, to immediately desilence HCMV MIE genes. This signaling cascade is distinctly different from that elicited by VIP.
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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.