Abstract
Type I interferon (IFN-I) is critical for a host against viral and bacterial infections via induction of hundreds of interferon-stimulated genes (ISGs), but the mechanism underlying the regulation of IFN-I remains largely unknown. In this study, we first demonstrate that ISG expression is required for optimal IFN-β levels, an effect that is further enhanced by endoplasmic reticulum (ER) stress. Furthermore, we identify mitochondrial calcium uniporter protein (MCU) as a mitochondrial antiviral signaling protein (MAVS)-interacting protein that is important for ER stress induction and amplified MAVS signaling activation. In addition, by performing an ectopic expression assay to screen a library of 117 human ISGs for effects on IFN-β levels, we found that tumor necrosis factor receptor 1 (TNFR1) significantly increases IFN-β levels independent of ER stress. Altogether, our findings suggest that MCU and TNFR1 are involved in the regulation of RIG-I-like receptors (RLR) signaling.
Highlights
The robust and rapid induction of IFN-I is important for a host in protection against viral and bacterial infections[1]
We found that MAVS co-localized with Tom[20], suggesting that MAVS is expressed on mitochondria in HeLa cells (Fig. 1A), consistent with a previous report[4]
We observed that the deletion of MAVS abolished poly(I:C)-induced IFN-β expression (Fig. 1B) and downstream IFN-stimulated genes (ISGs) levels, including those of 2′,5′ -oligoadenylate synthetase 1 (OAS1) and protein kinase R (PKR) (Fig. 1C,D)
Summary
The robust and rapid induction of IFN-I is important for a host in protection against viral and bacterial infections[1]. We addressed whether ISG expression regulates IFN-β through ER stress by constructing a GFP-tagged XBP-1 plasmid and transfecting it into HeLa cells. Poly(I:C) or thapsigargin (TG, a specific ER stress inducer) treatment significantly increased the number of GFP-positive cells (Fig. 1G,H).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
