Journalartikel

Induction of Interferon Synthesis by the PKR-Inhibitory VA RNAs of Adenoviruses


AutorenlisteWeber, F; Wagner, V; Kessler, N; Haller, O

Jahr der Veröffentlichung2006

Seiten1-7

ZeitschriftJournal of Interferon and Cytokine Research

Bandnummer26

Heftnummer1

ISSN1079-9907

DOI Linkhttps://doi.org/10.1089/jir.2006.26.1

VerlagMary Ann Liebert


Abstract
In virus-infected cells, double-stranded RNA ( dsRNA) activates the transcription factor interferon (IFN) regulatory factor-3 (IRF-3), which stimulates type I IFN (IFN-alpha/beta) gene expression. In addition, dsRNA activates the enzyme RNA-activated protein kinase (PKR), which phosphorylates the eukaryotic initiation factor 2 alpha (eIF2 alpha), thereby inhibiting mRNA translation. Adenoviruses express highly structured RNA molecules termed VA RNAs (VA(I)/VA(II)) known to specifically inhibit PKR. As PKR impairs expression from transfected cDNA constructs, plasmids encoding VA RNAs are widely used as enhancers of transgene expression. Here, we describe induction of IFN synthesis as a novel feature of VA RNAs. Transfection of a VA(I)/VA(II)-expressing plasmid was found to induce type I IFN production, resulting in activation of IFN-dependent genes, such as IFN-stimulated gene 56 (ISG56) or MxA, and the establishment of an antiviral state in transfected cells. Curiously, VA RNAs did not activate IRF-3, suggesting an alternative pathway of IFN induction. These data may be considered when using genetically modified adenoviruses as therapeutic agents and suggest caution in choosing VA RNA constructs as a means to increase expression of a gene of interest.



Zitierstile

Harvard-ZitierstilWeber, F., Wagner, V., Kessler, N. and Haller, O. (2006) Induction of Interferon Synthesis by the PKR-Inhibitory VA RNAs of Adenoviruses, Journal of Interferon and Cytokine Research, 26(1), pp. 1-7. https://doi.org/10.1089/jir.2006.26.1

APA-ZitierstilWeber, F., Wagner, V., Kessler, N., & Haller, O. (2006). Induction of Interferon Synthesis by the PKR-Inhibitory VA RNAs of Adenoviruses. Journal of Interferon and Cytokine Research. 26(1), 1-7. https://doi.org/10.1089/jir.2006.26.1


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