Regulation of type I interferon responses

Abstract

Type I interferons (IFNs) activate intracellular antimicrobial programmes and influence the development of innate and adaptive immune responses. Canonical type I IFN signalling activates the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway, leading to transcription of IFN-stimulated genes (ISGs). Host, pathogen and environmental factors regulate the responses of cells to this signalling pathway and thus calibrate host defences while limiting tissue damage and preventing autoimmunity. Here, we summarize the signalling and epigenetic mechanisms that regulate type I IFN-induced STAT activation and ISG transcription and translation. These regulatory mechanisms determine the biological outcomes of type I IFN responses and whether pathogens are cleared effectively or chronic infection or autoimmune disease ensues.

Function of HNRNPC in breast cancer cells by controlling the dsRNA‐induced interferon response

“…In response to this binding signal, the JAK‐STAT pathway is activated, leading to transcriptional up‐regulation of the ISGs (Ivashkiv & Donlin, 2014; Schneider et al , 2014). Therefore, to show that the up‐regulated ISGs upon HNRNPC knock‐down depend on the interferon signaling cascade, we used an IFNβ antibody, an IFNAR2 blocking antibody, and the JAK‐STAT inhibitor ruxolitinib to block the interferon signaling pathway at different levels.…”

Ebolavirus evolves in human to minimize the detection by immune cells by accumulating adaptive mutations

“…In addition, VP24 prevents the nuclear accumulation of dimerized phosphorylated STAT-1 that participates in activation of both type I and type II signalling cascades [13,23,27]. It is possible that the negatively selected VP24 sites, 55 and 133, might aid the EBOV to become more pathogenic to human by inhibiting IFN response and blocking antigen presentation to T-cells [18].…”

Expression characterization, genomic structure and function analysis of fish ubiquitin-specific protease 18 (USP18) genes

“…Upon viral infection, virus components are recognized by host pattern recognition receptors (PRRs) including Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) (Ivashkiv and Donlin, 2014). Such recognition events trigger distinct signaling pathways and finally activate the common transcription factors, mainly including IFN-regulatory factor 3 and/or 7, to initiate the transcription of type I IFNs.…”

“…Such recognition events trigger distinct signaling pathways and finally activate the common transcription factors, mainly including IFN-regulatory factor 3 and/or 7, to initiate the transcription of type I IFNs. The secreted type I IFNs exert their biological effects through induction of numerous IFNstimulated genes (ISGs) by the Janus kinase (Jak)-signal transducer and activator of the transcription (Stat) signaling pathway, where a transcription factor complex IFN-stimulated gene factor 3 (ISGF3) is formed, translocates to nucleus and specifically binds to the IFNstimulated response elements (ISREs) in the promoters of ISGs (Ivashkiv and Donlin, 2014). Although type I IFN response is essential for inhibition of viral infection, IFN overproduction is harmful to host and might result in several autoimmune diseases (Ivashkiv and Donlin, 2014).…”