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MAP Kinase-Mediated Licensing of Interferon Regulatory Factor (IRF) 3/7 Reinforces the Cell Response to Virus.

J Biol Chem.. 2013-11; 
S Schmid, D Sachs. Icahn School of Medicine at Mount Sinai, United States.
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Abstract

The induction of the intrinsic antiviral defense in mammals relies on the accumulation of foreign genetic material. As such, complete engagement of this response is limited to replication-competent viruses. Interferon regulatory factors (IRFs) are mediators of this defense with shared enhancer elements but display a spectrum of transcriptional potential. Here we describe a mechanism designed to enhance this response should a pathogen not be successfully inhibited. We find that activation of IRF7 results in the induction of MAP3K8 and restructuring of the antiviral transcriptome. MAP3K8 mediates the phosphorylation and repression of IRF3 homodimers to promote greater transcriptional activity through utilization ... More

Keywords

Cellular immune response; Dimer formation; IRF3; IRF7; MAP kinases (MAPKs); PML-nuclear bodies; Protein phosphorylation; SP100; Transcriptomics; Virus