ArticleJournal of virology1998
Inhibition of NF-kappaB activation in combination with bcl-2 expression allows for persistence of first-generation adenovirus vectors in the mouse liver.
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 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 74 citations in OpenAlex.
- Retargeting adenoviruses for therapeutic applications and vaccines.FEBS letters · 2020Review
- Suppression of Oncolytic Adenovirus-Mediated Hepatotoxicity by Liver-Specific Inhibition of NF-κB.Molecular therapy oncolytics · 2017Article
- NF-κB promotes leaky expression of adenovirus genes in a replication-incompetent adenovirus vector.Scientific reports · 2016Article
- Article
- GammadeltaT cells initiate acute inflammation and injury in adenovirus-infected liver via cytokine-chemokine cross talk.Journal of virology · 2008Article
- B5-deficient vaccinia virus as a vaccine vector for the expression of a foreign antigen in vaccinia immune animals.Virology · 2007Article
- Adenovirus binding to blood factors results in liver cell infection and hepatotoxicity.Journal of virology · 2005Article
- Evaluation of biodistribution and safety of adenovirus vectors containing group B fibers after intravenous injection into baboons.Human gene therapy · 2005Article
- Analysis of adenovirus sequestration in the liver, transduction of hepatic cells, and innate toxicity after injection of fiber-modified vectors.Journal of virology · 2004Article
- Simple and effective osteoinductive gene therapy by local injection of a bone morphogenetic protein-2-expressing recombinant adenoviral vector and FK506 mixture in rats.Gene therapy · 2004Article
- Adenovirus expression of IL-1 and NF-kappaB inhibitors does not inhibit acute adenoviral-induced brain inflammation, but delays immune system-mediated elimination of transgene expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2003Article
- Adaptive and innate immune responses to gene transfer vectors: role of cytokines and chemokines in vector function.Gene therapy · 2003Review
- Modulation of hepatic granulomatous responses by transgene expression of DAP12 or TREM-1-Ig molecules.The American journal of pathology · 2003Article
- Coexpression of p21(WAF1/CIP1) in adenovirus vector transfected human primary hepatocytes prevents apoptosis resulting in improved transgene expression.Gene therapy · 2003Article
- Potentiation of chemotherapeutic agents following antagonism of nuclear factor kappa B in human gliomas.Journal of neuro-oncology · 2003Article
- Inhibition of tumor necrosis factor alpha-induced NF-kappa B activation by the adenovirus E3-10.4/14.5K complex.Journal of virology · 2002Article
- A high-capacity, capsid-modified hybrid adenovirus/adeno-associated virus vector for stable transduction of human hematopoietic cells.Journal of virology · 2002Article
- Activation of NF-kB mediates ICAM-1 induction in respiratory cells exposed to an adenovirus-derived vector.Gene therapy · 2001Article
- Recombinant adenovirus induces maturation of dendritic cells via an NF-kappaB-dependent pathway.Journal of virology · 2000Article
- Efficient gene transfer into human CD34(+) cells by a retargeted adenovirus vector.Journal of virology · 2000Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
NF-kappaB is a key regulator of the innate antiviral immune response, due in part to its transcriptional activation of cytokines and adhesion molecules, which, in turn, function in chemotaxis and activation of inflammatory cells. We reported earlier that viral gene expression in hepatocytes transduced with first-generation (E1-deleted) adenoviruses induced NF-kappaB activation, elevation of serum cytokines, and hepatocellular apoptosis during the first days postinfusion. These events did not occur in mice infused with an adenovirus vector deleted for E1, E2, E3, and late gene expression. In the present study, we used an adenovirus expressing an IkappaBalpha supersuppressor (Ad.IkappaBM) and bcl-2 transgenic mice to unravel the role of virus-induced NF-kappaB activation and apoptosis in the clearance of recombinant adenovirus vectors from the liver. The combined action of IkappaBM and Bcl-2 allowed for vector persistence in livers of C57BL/6 x C3H mice. In the absence of Bcl-2, IkappaBM expression in mouse livers significantly reduced NF-kappaB activation, cytokine expression, leukocyte infiltration, and the humoral immune response against the transgene product; however, this was not sufficient to prevent the decline of vector DNA in transduced cells. Infusion of Ad.IkappaBM caused extended apoptosis predominantly in periportal liver regions, indicating that NF-kappaB activation may protect transduced hepatocytes from apoptosis induced by adenovirus gene products. To confer vector persistence, bcl-2 transgene expression was required to block virus-induced apoptosis if NF-kappaB protection was inactivated by IkappaBM. Expression of gene products involved in early stages of apoptotic pathways was up-regulated in response to virus infusion in bcl-2 transgenic mice, which may represent a compensatory effect. Our study supports the idea that the suppression of innate defense mechanisms improves vector persistence.
Indexed as
Identifiers
What OpenQuestion holds
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.