ArticlePLoS pathogens2016
PKR Transduces MDA5-Dependent Signals for Type I IFN Induction.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 110 citations in OpenAlex.
- Safety, pharmacokinetics, and pharmacodynamics of human interferon-α2b spray in healthy participants.Antimicrobial agents and chemotherapy · 2025Trial
- Key role of TLR3 in type I IFN expression and apoptosis induction in IBDV-infected chicken fibroblast cells.Frontiers in cellular and infection microbiology · 2026Article
- IFN alpha inducible protein 27 (IFI27) acts as a positive regulator of PACT-dependent PKR activation after RNA virus infections.PLoS pathogens · 2025Article
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- RNA sensing at the crossroads of autoimmunity and autoinflammation.RNA (New York, N.Y.) · 2025Review
- Redox phenotype confers T cell-exclusion microenvironment and resistance to immunotherapy by suppressingFrontiers in oncology · 2025Article
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- Functional Analysis of Oligoadenylate Synthetase in the Emu (Animals : an open access journal from MDPI · 2024Article
- Nucleic acid-induced inflammation on hematopoietic stem cells.Experimental hematology · 2024Article
- Innate immune responses to RNA: sensing and signaling.Frontiers in immunology · 2024Review
- A little less aggregation a little more replication: Viral manipulation of stress granules.Wiley interdisciplinary reviews. RNA · 2023Review
- Poxviruses and the immune system: Implications for monkeypox virus.International immunopharmacology · 2022Review
- DYT-Biomolecules · 2022Article
- Cytoplasmic RNA sensors and their interplay with RNA-binding partners in innate antiviral response: theme and variations.RNA (New York, N.Y.) · 2022Review
- A tale of two proteins: PACT and PKR and their roles in inflammation.The FEBS journal · 2021Review
- Protein kinase R and the integrated stress response drive immunopathology caused by mutations in the RNA deaminase ADAR1.Immunity · 2021Article
- Battle Royale: Innate Recognition of Poxviruses and Viral Immune Evasion.Biomedicines · 2021Review
- The Role of Coronavirus RNA-Processing Enzymes in Innate Immune Evasion.Life (Basel, Switzerland) · 2021Review
- Echinacea purpurea (L.) Moench treatment of monocytes promotes tonic interferon signaling, increased innate immunity gene expression and DNA repeat hypermethylated silencing of endogenous retroviral sequences.BMC complementary medicine and therapies · 2021Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Sensing invading pathogens early in infection is critical for establishing host defense. Two cytosolic RIG-like RNA helicases, RIG-I and MDA5, are key to type I interferon (IFN) induction in response to viral infection. Mounting evidence suggests that another viral RNA sensor, protein kinase R (PKR), may also be critical for IFN induction during infection, although its exact contribution and mechanism of action are not completely understood. Using PKR-deficient cells, we found that PKR was required for type I IFN induction in response to infection by vaccinia virus lacking the PKR antagonist E3L (VVΔE3L), but not by Sendai virus or influenza A virus lacking the IFN-antagonist NS1 (FluΔNS1). IFN induction required the catalytic activity of PKR, but not the phosphorylation of its principal substrate, eIF2α, or the resulting inhibition of host translation. In the absence of PKR, IRF3 nuclear translocation was impaired in response to MDA5 activators, VVΔE3L and encephalomyocarditis virus, but not during infection with a RIG-I-activating virus. Interestingly, PKR interacted with both RIG-I and MDA5; however, PKR was only required for MDA5-mediated, but not RIG-I-mediated, IFN production. Using an artificially activated form of PKR, we showed that PKR activity alone was sufficient for IFN induction. This effect required MAVS and correlated with IRF3 activation, but no longer required MDA5. Nonetheless, PKR activation during viral infection was enhanced by MDA5, as virus-stimulated catalytic activity was impaired in MDA5-null cells. Taken together, our data describe a critical and non-redundant role for PKR following MDA5, but not RIG-I, activation to mediate MAVS-dependent induction of type I IFN through a kinase-dependent mechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.