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Synthetic rewiring and boosting type I interferon responses for visualization and counteracting viral infections.
Gödecke, Natascha Riedel, Jan Herrmann, Sabrina Behme, Sara Rand, Ulfert Kubsch, Tobias Cicin-Sain, Luka Hauser, Hansjörg Köster, Mario Wirth, Dagmar
Gödecke, Natascha
Riedel, Jan
Herrmann, Sabrina
Behme, Sara
Rand, Ulfert
Kubsch, Tobias
Cicin-Sain, Luka
Hauser, Hansjörg
Köster, Mario
Wirth, Dagmar
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2020-11-18
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Abstract
Mammalian first line of defense against viruses is accomplished by the interferon (IFN) system. Viruses have evolved numerous mechanisms to reduce the IFN action allowing them to invade the host and/or to establish latency. We generated an IFN responsive intracellular hub by integrating the synthetic transactivator tTA into the chromosomal Mx2 locus for IFN-based activation of tTA dependent expression modules. The additional implementation of a synthetic amplifier module with positive feedback even allowed for monitoring and reacting to infections of viruses that can antagonize the IFN system. Low and transient IFN amounts are sufficient to trigger these amplifier cells. This gives rise to higher and sustained-but optionally de-activatable-expression even when the initial stimulus has faded out. Amplification of the IFN response induced by IFN suppressing viruses is sufficient to protect cells from infection. Together, this interfaced sensor/actuator system provides a toolbox for robust sensing and counteracting viral infections.
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Nucleic Acids Res. 2020 Nov 18;48(20):11799-11811. doi: 10.1093/nar/gkaa961.
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Article
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en
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1362-4962
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Attribution-NonCommercial-ShareAlike 4.0 International