Journal article

Authors list: Weber, F; Wagner, V; Kessler, N; Haller, O

Publication year: 2006

Pages: 1-7

Journal: Journal of Interferon and Cytokine Research

Volume number: 26

Issue number: 1

ISSN: 1079-9907

DOI Link: https://doi.org/10.1089/jir.2006.26.1

Publisher: Mary 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.

Harvard Citation style: Weber, 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 Citation style: Weber, 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