ArticleJournal of virology1998
Reactivation of the previously silenced cytomegalovirus major immediate-early promoter in the mouse liver: involvement of NFkappaB.
Article in Journal of virology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 281 citations in OpenAlex.
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- Polymeric nanoparticles for dual-targeted theranostic gene delivery to hepatocellular carcinoma.Science advances · 2022Article
- miR-AB, a miRNA-based shRNA viral toolkit for multicolor-barcoded multiplex RNAi at a single-cell level.EMBO reports · 2022Article
- Selective transduction of cerebellar Purkinje and granule neurons using delivery of AAV-PHP.eB and AAVrh10 vectors at axonal terminal locations.Frontiers in molecular neuroscience · 2022Article
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- Impact of cytomegalovirus load on host response to sepsis.Medical microbiology and immunology · 2019Review
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- Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model.Human gene therapy. Clinical development · 2018Article
- Rescue of GSDIII Phenotype with Gene Transfer Requires Liver- and Muscle-Targeted GDE Expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- AAV2-Mediated Transduction of the Mouse Retina After Optic Nerve Injury.Investigative ophthalmology & visual science · 2017Article
- Inflammasome expression and cytomegalovirus viremia in critically ill patients with sepsis.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2017Observational
- Stable In Vivo Transgene Expression in Endothelial Cells with Helper-Dependent Adenovirus: Roles of Promoter and Interleukin-10.Human gene therapy · 2017Article
- Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytomegalovirus (CMV) major immediate-early promoter/enhancer is active in many cell culture systems and is considered to be one of the strongest promoters in vitro. However, when this promoter was used in in vivo approaches to gene therapy, it was silenced within a few weeks in several organs including the liver. In this study, we demonstrated transcriptional inactivation of the CMV promoter in mouse liver. In contrast to the CMV promoter, a hybrid promoter consisting of a minimal CMV promoter and the enhancer II of hepatitis B virus was active for at least 11 weeks in mouse liver. While investigating the reason for the shutdown of the CMV promoter, we did not find evidence for methylation of adenovirus DNA in the region of transgene insertion, but we could show that the silenced CMV promoter was reactivated after lipopolysaccharide treatment of mice or partial hepatectomy. Both stimuli are known to activate the transcription factor NFkappaB, which binds to four sites in the CMV promoter/enhancer. We show that expression from the CMV promoter in hepatocyte-derived cell lines in vitro depends on NFkappaB. In vivo experiments demonstrate that NFkappaB, which is not present in mouse hepatocytes in vivo, is activated after infection with recombinant adenoviruses and that the time course of NFkappaB activation parallels that of CMV promoter-dependent expression. Moreover, adenovirus infection of transgenic mice carrying a CMV promoter-driven lacZ gene leads to strong activation of the expression of this gene in the liver. Thus, NFkappaB is involved in the activation of the CMV promoter in the liver.
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