ArticleThe Journal of general virology2009
PKR acts early in infection to suppress Semliki Forest virus production and strongly enhances the type I interferon response.
Article in The Journal of general virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
- Sequence Diversity in the 3' Untranslated Region of Alphavirus Modulates IFIT2-Dependent Restriction in a Cell Type-Dependent Manner.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- Prior influenza virus infection alleviates an arbovirus encephalitis by reducing viral titer, inflammation, and cellular infiltrates in the central nervous system.Journal of virology · 2025Article
- Next generation self-replicating RNA vectors for vaccines and immunotherapies.Cancer gene therapy · 2023Review
- Immunogenic cell death triggered by impaired deubiquitination in multiple myeloma relies on dysregulated type I interferon signaling.Frontiers in immunology · 2023Article
- Distinct Cellular Tropism and Immune Responses to Alphavirus Infection.Annual review of immunology · 2022Review
- Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases.Cells · 2022Review
- DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice.Scientific reports · 2021Article
- Induction of UPR Promotes Interferon Response to Inhibit PRRSV ReplicationFrontiers in microbiology · 2021Article
- Novel Mutations in nsP2 Abolish Chikungunya Virus-Induced Transcriptional Shutoff and Make the Virus Less Cytopathic without Affecting Its Replication Rates.Journal of virology · 2019Article
- Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis.The Journal of general virology · 2019Article
- Contribution of the Unfolded Protein Response (UPR) to the Pathogenesis of Proteasome-Associated Autoinflammatory Syndromes (PRAAS).Frontiers in immunology · 2019Review
- ADAR1: "Editor-in-Chief" of Cytoplasmic Innate Immunity.Frontiers in immunology · 2019Review
- Innate immune control of alphavirus infection.Current opinion in virology · 2018Review
- RIPK3 interacts with MAVS to regulate type I IFN-mediated immunity to Influenza A virus infection.PLoS pathogens · 2017Article
- Article
- PKR Activation Favors Infectious Pancreatic Necrosis Virus Replication in Infected Cells.Viruses · 2016Article
- PKR Transduces MDA5-Dependent Signals for Type I IFN Induction.PLoS pathogens · 2016Article
- PKR deficiency alters E. coli-induced sickness behaviors but does not exacerbate neuroimmune responses or bacterial load.Journal of neuroinflammation · 2015Article
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The double-stranded RNA-activated protein kinase (PKR) is a key regulator of protein translation, interferon (IFN) expression and cell survival. Upon infection of vertebrate cells in continuous culture, the alphavirus Semliki Forest virus (SFV) initiates apoptosis and IFN synthesis. To determine the effect of PKR on SFV infection, we studied the course of infection in wild-type (wt) mice, mice with a genetic deletion of PKR (PKR-/-) and mouse embryo fibroblasts (MEFs) derived from these mice. In MEFs, PKR delayed virus protein synthesis, production of infectious virus and caspase-3-activated cell death and reduced the yield of infectious virus by 90%. Small interfering RNA suppression of PKR levels in NIH-3T3 cells also reduced virus production and apoptosis. In MEFs, PKR was not required for initiation of IFN-beta gene transcription, but contributed strongly to the magnitude of this response. Levels of IFN-beta transcripts in PKR-/- MEFs at 8 h were 80% lower than those in wt MEFs and levels of functional IFN at 24 h were 95% lower. Following infection of wt and PKR-/- mice, SFV4 and SFV A7(74) were avirulent. PKR increased levels of serum IFN and the rate of clearance of infectious virus from the brain. In summary, in response to SFV, PKR exerts an early antiviral effect that delays virus protein production and release of infectious virus and, whilst PKR is not required for induction of apoptosis or activation of the type I IFN response, it strongly augments the type I IFN response and contributes to clearance of infectious virus from the mouse brain.
Indexed as
Identifiers
What OpenQuestion holds
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.