We have located links that may give you full text access.
Activation of protein kinase receptor (PKR) plays a pro-viral role in mammarenavirus-infected cells.
Journal of Virology 2024 Februrary 21
Many viruses, including mammarenaviruses, have evolved mechanisms to counteract different components of the host cell innate immunity, which is required to facilitate robust virus multiplication. The double-stranded RNA (dsRNA) sensor protein kinase receptor (PKR) pathway plays a critical role in the cell anti-viral response. Whether PKR can restrict the multiplication of the Old World mammarenavirus lymphocytic choriomeningitis virus (LCMV) and the mechanisms by which LCMV may counteract the anti-viral functions of PKR have not yet been investigated. Here we present evidence that LCMV infection results in very limited levels of PKR activation, but LCMV multiplication is enhanced in the absence of PKR. In contrast, infection with a recombinant LCMV with a mutation affecting the 3'-5' exonuclease (ExoN) activity of the viral nucleoprotein resulted in robust PKR activation in the absence of detectable levels of dsRNA, which was associated with severely restricted virus multiplication that was alleviated in the absence of PKR. However, pharmacological inhibition of PKR activation resulted in reduced levels of LCMV multiplication. These findings uncovered a complex role of the PKR pathway in LCMV-infected cells involving both pro- and anti-viral activities.IMPORTANCEAs with many other viruses, the prototypic Old World mammarenavirus LCMV can interfere with the host cell innate immune response to infection, which includes the dsRNA sensor PKR pathway. A detailed understanding of LCMV-PKR interactions can provide novel insights about mammarenavirus-host cell interactions and facilitate the development of effective anti-viral strategies against human pathogenic mammarenaviruses. In the present work, we present evidence that LCMV multiplication is enhanced in PKR-deficient cells, but pharmacological inhibition of PKR activation unexpectedly resulted in severely restricted propagation of LCMV. Likewise, we document a robust PKR activation in LCMV-infected cells in the absence of detectable levels of dsRNA. Our findings have revealed a complex role of the PKR pathway during LCMV infection and uncovered the activation of PKR as a druggable target for the development of anti-viral drugs against human pathogenic mammarenaviruses.
Full text links
Related Resources
Trending Papers
Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.Endocrine Reviews 2024 April 28
The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.Circulation 2024 April 26
British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults.Gut 2024 April 17
Interstitial Lung Disease: A Review.JAMA 2024 April 23
Ventilator Waveforms May Give Clues to Expiratory Muscle Activity.American Journal of Respiratory and Critical Care Medicine 2024 April 25
Systemic lupus erythematosus.Lancet 2024 April 18
Acute Kidney Injury and Electrolyte Imbalances Caused by Dapagliflozin Short-Term Use.Pharmaceuticals 2024 March 27
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app