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Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
Published on: July 29, 2014
Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection
S Balachandran1, P C Roberts, L E Brown
1Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33136, USA.
Abstract:
The double-stranded (ds) RNA-dependent protein kinase PKR is considered to play an important role in interferon's (IFN's) response to viral infection. Here, we demonstrate that mice lacking PKR are predisposed to lethal intranasal infection by the usually innocuous vesicular stomatitis virus, and also display increased susceptibility to influenza virus infection. Our data indicate that in normal cells, PKR primarily prevents virus replication by inhibiting the translation of viral mRNAs through phosphorylation of eIF2alpha, while concomitantly assisting in the production of autocrine IFN and the establishment of an antiviral state. These results show that PKR is an essential component of innate immunity that acts early in host defense prior to the onset of IFN counteraction and the acquired immune response.
Insights
The protein kinase PKR is crucial for innate immunity against viruses. Mice lacking PKR show increased susceptibility to viral infections, highlighting its early host defense role.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- The double-stranded RNA-dependent protein kinase PKR is implicated in the interferon (IFN) response to viral infections.
- Its precise role in early host defense against common viruses is not fully elucidated.
Purpose of the Study:
- To investigate the role of PKR in innate immunity against viral infections.
- To determine the mechanisms by which PKR mediates antiviral defense.
Main Methods:
- Utilized a mouse model lacking the PKR gene.
- Assessed susceptibility to intranasal infection with vesicular stomatitis virus and influenza virus.
- Investigated viral mRNA translation inhibition and autocrine IFN production in PKR-deficient cells.
Main Results:
- Mice lacking PKR exhibited lethal susceptibility to vesicular stomatitis virus and increased susceptibility to influenza virus.
- PKR was found to inhibit viral mRNA translation via eIF2alpha phosphorylation.
- PKR also promoted autocrine IFN production and established an antiviral state.
Conclusions:
- PKR is an essential component of innate immunity, acting early in host defense.
- PKR prevents viral replication by inhibiting translation and promoting IFN production.
- These findings underscore PKR's critical role before adaptive immunity is engaged.
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