Antiviral interferon-beta signaling induced by designed transcription activator-like effectors (TALE).

Ivonne Renner,Rene Geissler,Nancy Funk,Anika Penzel,Sven-Erik Behrens,Susann Friedrich,Matthias J Schnell

doi:10.1371/journal.pone.0114288

Ivonne Renner, Rene Geissler + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0114288

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Journal: PloS one	Publication Date: Dec 3, 2014
Citations: 3	License type: CC BY 4.0

Affiliation: Martin Luther University Halle-Wittenberg

Abstract

Here we show that designed transcription activator-like effectors (TALEs) that bind to defined areas of the interferon beta promoter are capable to induce IFN-beta expression and signaling in human cells. Importantly, TALE-mediated IFN-beta signaling occurs independently of pathogen pattern recognition but effectively prohibits viral RNA replication as demonstrated with a hepatitis C virus replicon. TALEs were thus indicated to be valuable tools in various applications addressing, for example, virus-host interactions.

Highlights

transcription activator-like effectors (TALEs) were originally characterized as virulence factors of plant pathogenic bacteria that reprogram gene transcription of the host cells
Following earlier work, which revealed the general option to induce IFN-beta expression in human cells by a TALE [5], this study aimed at investigating if an entire antiviral IFN-beta signaling cascade may be navigated by designed effectors
After transient transfection of the expression plasmids, all six effectors were comparably expressed in Huh7 cells. This was demonstrated by western-blot that detected the TALEs via a fused green fluorescent protein (GFP) reporter (Fig. 1B)

Summary

Introduction

TALEs were originally characterized as virulence factors of plant pathogenic bacteria that reprogram gene transcription of the host cells. TALEs contain a DNA binding domain that is composed of similar tandem repeats of typically 34 amino acids. Each repeat binds one base pair of the target DNA, and a repeat-variable di-residue (RVD) specifies the bound base [1,2,3,4]. ‘designer TALEs’ containing a defined order of repeats and a suitable transcription activation domain can be constructed and applied to induce the transcription of human genes [5,6,7]. An attractive target for transcription activation is the cytokine IFN-beta, which is well characterized regarding its antiviral activity and used during treatment of multiple sclerosis [8, 9]. The IFN-beta promoter mainly consists of an enhancer that is flanked by two nucleosomes, one masking the transcriptional TATA-box (Fig. 1A)

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