Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression
1
Institute of Genetics, Technische Universität Braunschweig, 38106 Braunschweig, Germany
2
Viral Immune Modulation Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(7), 733; https://doi.org/10.3390/v12070733
Received: 15 June 2020 / Revised: 3 July 2020 / Accepted: 3 July 2020 / Published: 7 July 2020
(This article belongs to the Special Issue Innate Immune Sensing of Viruses and Viral Evasion)
The type I interferon (IFN) response is a principal component of our immune system that allows to counter a viral attack immediately upon viral entry into host cells. Upon engagement of aberrantly localised nucleic acids, germline-encoded pattern recognition receptors convey their find via a signalling cascade to prompt kinase-mediated activation of a specific set of five transcription factors. Within the nucleus, the coordinated interaction of these dimeric transcription factors with coactivators and the basal RNA transcription machinery is required to access the gene encoding the type I IFN IFNβ (IFNB1). Virus-induced release of IFNβ then induces the antiviral state of the system and mediates further mechanisms for defence. Due to its key role during the induction of the initial IFN response, the activity of the transcription factor interferon regulatory factor 3 (IRF3) is tightly regulated by the host and fiercely targeted by viral proteins at all conceivable levels. In this review, we will revisit the steps enabling the trans-activating potential of IRF3 after its activation and the subsequent assembly of the multi-protein complex at the IFNβ enhancer that controls gene expression. Further, we will inspect the regulatory mechanisms of these steps imposed by the host cell and present the manifold strategies viruses have evolved to intervene with IFNβ transcription downstream of IRF3 activation in order to secure establishment of a productive infection.
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Keywords:
interferon regulatory factor; IRF3; innate immunity; antiviral response; immune modulation; viral evasion; antagonist; interferon beta; enhanceosome; NF-κB
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MDPI and ACS Style
Schwanke, H.; Stempel, M.; Brinkmann, M.M. Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression. Viruses 2020, 12, 733.
AMA Style
Schwanke H, Stempel M, Brinkmann MM. Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression. Viruses. 2020; 12(7):733.
Chicago/Turabian StyleSchwanke, Hella; Stempel, Markus; Brinkmann, Melanie M. 2020. "Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression" Viruses 12, no. 7: 733.
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