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  • Interleukin-24 inhibits influenza A virus replication in vitro through induction of toll-like receptor 3 dependent apoptosis.

Interleukin-24 inhibits influenza A virus replication in vitro through induction of toll-like receptor 3 dependent apoptosis.

Antiviral research (2015-09-15)
René Weiss, Johannes Laengle, Monika Sachet, Anna-Polina Shurygina, Oleg Kiselev, Andrej Egorov, Michael Bergmann
ABSTRACT

New anti-viral agents and strategies are urgently needed to fight rapidly mutating viruses, as vaccine programs cannot react fast enough to prevent pandemics. Recently, we have shown that interleukin-24 (IL-24) sensitizes tumor cells to toll-like receptor 3 (TLR3) mediated apoptosis. As influenza A virus stimulates the TLR3 receptor, we hypothesized that IL-24 might also exert an anti-viral effect. This study demonstrates that IL-24 reduces the titer of different influenza A virus subtypes independently of type I interferon in an apoptosis dependent manner. The anti-viral effect of IL-24 correlated with caspase-3 activation and could be blocked by a pan-caspase inhibitor and by small interfering RNA (siRNA) directed towards TLR3. Surprisingly, caspase-3 activation in influenza A virus/IL-24-stimulated cells correlated with the down-regulation of the B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia 1 (Mcl-1). Correspondingly, knockdown of Mcl-1 by siRNA enhanced caspase activation in influenza A virus infected cells and was furthermore linked to a reduction of viral titers. We conclude that IL-24 exerts an anti-viral role selectively purging virally infected cells by leading to a down-regulation of Mcl-1. Our findings might therefore represent the first step towards a new rational concept in the development of anti-viral strategies based on the induction of apoptosis.

MATERIALS
Product Number
Brand
Product Description

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MISSION® esiRNA, targeting human TLR3
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IL-24 human, recombinant, expressed in CHO cells, ≥95% (SDS-PAGE), ≥95% (HPLC)
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Tris(tert-butoxy)silanol, 99.999%
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Propidium iodide, ≥94.0% (HPLC)
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IL-24 human, recombinant, expressed in Saccharomyces cerevisiae, ≥98% (SDS-PAGE), ≥98% (HPLC)
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Phenylacetic acid, 99%
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Propidium iodide solution
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Fluorescein 5(6)-isothiocyanate, ≥90% (HPLC)
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