ArticleJournal of virology2009
Breaking human cytomegalovirus major immediate-early gene silence by vasoactive intestinal peptide stimulation of the protein kinase A-CREB-TORC2 signaling cascade in human pluripotent embryonal NTera2 cells.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Sensing the storm: how inflammatory signalling drives reactivation of the human cytomegalovirus major immediate-early promoter.The Journal of general virology · 2026Review
- Cell type differences in human cytomegalovirus transcription and epigenetic regulation with insights into major immediate-early enhancer-promoter control.PLoS pathogens · 2025Article
- Phospho-proteomics identifies a critical role of ATF2 in pseudorabies virus replication.Virologica Sinica · 2022Article
- iTRAQ-Based Proteomics Analysis of Human Cytomegalovirus Latency and Reactivation in T98G Cells.Journal of virology · 2022Article
- CMV-encoded GPCR pUL33 activates CREB and facilitates its recruitment to the MIE locus for efficient viral reactivation.Journal of cell science · 2021Article
- Activator protein-1 transactivation of the major immediate early locus is a determinant of cytomegalovirus reactivation from latency.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- 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 IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II.PLoS pathogens · 2020Article
- Src family kinase activity drives cytomegalovirus reactivation by recruiting MOZ histone acetyltransferase activity to the viral promoter.The Journal of biological chemistry · 2019Article
- Alternative promoters drive human cytomegalovirus reactivation from latency.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Molecular Determinants and the Regulation of Human Cytomegalovirus Latency and Reactivation.Viruses · 2018Review
- Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency.Virology · 2017Article
- Cytomegalovirus latency and reactivation: recent insights into an age old problem.Reviews in medical virology · 2016Review
- 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
- Rapamycin does not inhibit human cytomegalovirus reactivation from dendritic cells in vitro.The Journal of general virology · 2014Article
- 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
- The intimate relationship between human cytomegalovirus and the dendritic cell lineage.Frontiers in microbiology · 2014Review
- Human cytomegalovirus infection of langerhans-type dendritic cells does not require the presence of the gH/gL/UL128-131A complex and is blocked after nuclear deposition of viral genomes in immature cells.Journal of virology · 2014Article
- Polycomb repressive complex 2 silences human cytomegalovirus transcription in quiescent infection models.Journal of virology · 2013Article
- Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The triggering mechanisms underlying reactivation of human cytomegalovirus (HCMV) in latently infected persons are unclear. During latency, HCMV major immediate-early (MIE) gene expression breaks silence to initiate viral reactivation. Using quiescently HCMV-infected human pluripotent embryonal NTera2 cells (NT2) to model HCMV reactivation, we show that vasoactive intestinal peptide (VIP), an immunomodulatory neuropeptide, immediately and dose-dependently (1 to 500 nM) activates HCMV MIE gene expression. This response requires the MIE enhancer cyclic AMP response elements (CRE). VIP quickly elevates CREB Ser133 and ATF-1 Ser63 phosphorylation levels, although the CREB Ser133 phosphorylation level is substantial at baseline. VIP does not change the level of HCMV genomes in nuclei, Oct4 (pluripotent cell marker), or hDaxx (cellular repressor of HCMV gene expression). VIP-activated MIE gene expression is mediated by cellular protein kinase A (PKA), CREB, and TORC2. VIP induces PKA-dependent TORC2 Ser171 dephosphorylation and nuclear entry, which likely enables MIE gene activation, as TORC2 S171A (devoid of Ser171 phosphorylation) exhibits enhanced nuclear entry and desilences the MIE genes in the absence of VIP stimulation. In conclusion, VIP stimulation of the PKA-CREB-TORC2 signaling cascade activates HCMV CRE-dependent MIE gene expression in quiescently infected NT2 cells. We speculate that neurohormonal stimulation via this signaling cascade is a possible means for reversing HCMV silence in vivo.
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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.