Abstract
As viruses have a capacity to rapidly evolve and continually alter the coding of their protein repertoires, host cells have evolved pathways to sense viruses through the one invariable feature common to all these pathogens—their nucleic acids. These genomic and transcriptional pathogen-associated molecular patterns (PAMPs) trigger the activation of germline-encoded anti-viral pattern recognition receptors (PRRs) that can distinguish viral nucleic acids from host forms by their localization and subtle differences in their chemistry. A wide range of transmembrane and cytosolic PRRs continually probe the intracellular environment for these viral PAMPs, activating pathways leading to the activation of anti-viral gene expression. The activation of Nuclear Factor Kappa B (NFκB) and Interferon (IFN) Regulatory Factor (IRF) family transcription factors are of central importance in driving pro-inflammatory and type-I interferon (TI-IFN) gene expression required to effectively restrict spread and trigger adaptive responses leading to clearance. Poxviruses evolve complex arrays of inhibitors which target these pathways at a variety of levels. This review will focus on how poxviruses target and inhibit PRR pathways leading to the activation of IRF family transcription factors.
Highlights
Germline-encoded pattern recognition receptors (PRRs) ‘sense’ infection by binding invariable chemical features of invading pathogens called pathogen-associated molecular patterns (PAMPs).Each PRR activates signal transduction pathways leading to gene expression, which orchestrates clearance of the specific type of pathogen from which the PAMP was derived
B (NFκB) and Interferon (IFN) Regulatory Factor (IRF) family transcription factors are of central importance in driving pro-inflammatory and type-I interferon (TI-IFN) gene expression required to effectively restrict spread and trigger adaptive responses leading to clearance
This review will focus on how poxviruses target and inhibit PRR pathways leading to the activation of IFN Regulatory Factor (IRF) family transcription factors
Summary
Germline-encoded pattern recognition receptors (PRRs) ‘sense’ infection by binding invariable chemical features of invading pathogens called pathogen-associated molecular patterns (PAMPs). Chordopoxvirinae subdivide into ten genera: orthopoxviruses, leporipoxviruses, yatapoxviruses, parapoxviruses, cervidpoxviruses, capripoxviruses, suipoxviruses, molluscipoxviruses, crocodylipoxviruses and avipoxviruses They can be grouped into four phylogenetic categories by order of divergence [7]. Poxviruses have well-characterized immunoevasive and immunomodulatory strategies to suppress activation of the host innate immune system, seeking to sense them in order to drive effector responses leading to their clearance [8] These strategies target signaling pathways at a variety of points in activation, with a preference for targeting downstream at common points of convergence in the activation of NFκB and IRF family transcription factors. We will discuss the strategies that poxviruses have evolved to target pathways leading to the activation of IRF-family transcription factors, with a focus on preventing the induction of TI-IFNs
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