2. Academic Validation
  3. NLRX1 promotes immediate IRF1-directed antiviral responses by limiting dsRNA-activated translational inhibition mediated by PKR

NLRX1 promotes immediate IRF1-directed antiviral responses by limiting dsRNA-activated translational inhibition mediated by PKR

  • Nat Immunol. 2017 Dec;18(12):1299-1309. doi: 10.1038/ni.3853.
Hui Feng 1 2,  Erik M Lenarcic 1 3,  Daisuke Yamane 1 2,  Eliane Wauthier 1 4,  Jinyao Mo 1 2,  Haitao Guo 1 5,  David R McGivern 1 2,  Olga González-López 1 2,  Ichiro Misumi 1 4,  Lola M Reid 1 5,  Jason K Whitmire 1 3 4,  Jenny P-Y Ting 1 4,  Joseph A Duncan 1 2 6,  Nathaniel J Moorman 1 3,  Stanley M Lemon 1 2 3
Affiliations

Affiliations

  • 1 Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 2 Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 3 Department of Microbiology & Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 4 Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 5 Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 6 Department of Pharmacology, The University of North Carolina, Chapel Hill, North Carolina, USA.
PMID: 28967880 DOI: 10.1038/ni.3853
Abstract

NLRX1 is unique among the nucleotide-binding-domain and leucine-rich-repeat (NLR) proteins in its mitochondrial localization and ability to negatively regulate Antiviral innate immunity dependent on the adaptors MAVS and STING. However, some studies have suggested a positive regulatory role for NLRX1 in inducing Antiviral responses. We found that NLRX1 exerted opposing regulatory effects on viral activation of the transcription factors IRF1 and IRF3, which might potentially explain such contradictory results. Whereas NLRX1 suppressed MAVS-mediated activation of IRF3, it conversely facilitated virus-induced increases in IRF1 expression and thereby enhanced control of viral Infection. NLRX1 had a minimal effect on the transcription of IRF1 mediated by the transcription factor NF-kB and regulated the abundance of IRF1 post-transcriptionally by preventing translational shutdown mediated by the double-stranded RNA (dsRNA)-activated kinase PKR and thereby allowed virus-induced increases in the abundance of IRF1 protein.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15005
    99.97%, HCV Inhibitor
    HCV