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Published on: May 24, 2020
PKR engages viral RNA and intron-retained host transcripts during poxvirus infection
Ruilin Zhang1, Xiang Ye1, Andrew C Dixson2
1Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Vanderbilt Center for Immunobiology, and Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, TN 37232-2363, USA.
Cell Reports
|August 8, 2026
Summary
Protein kinase R (PKR) detects viral RNA and host RNAs with retained introns during vaccinia virus infection. Defective RNA processing activates PKR, crucial for innate antiviral defense.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Double-stranded RNA (dsRNA) recognition is key to antiviral immunity.
- Mechanisms of RNA sensor activation during viral infections are not fully understood.
Purpose of the Study:
- To investigate the activation of Protein Kinase R (PKR) during vaccinia virus (VacV) infection.
- To identify the RNA species that activate PKR and the factors modulating its response.
Main Methods:
- Analysis of PKR binding to viral and host RNAs during VacV infection.
- Investigating the role of RNase L in pre-mRNA splicing and subsequent PKR activation.
- Utilizing small-molecule inhibitors to probe splicing-dependent PKR activation.
- Examining the influence of PACT and viral E3 on PKR signaling.
Main Results:
- PKR preferentially binds to viral RNAs and host intron-retaining transcripts during VacV infection.
- RNase L activation impairs pre-mRNA splicing, leading to cytoplasmic accumulation of intron-retaining RNAs.
- Splicing inhibition activates PKR independently of RNase L, indicating defective splicing as a PKR ligand source.
- PKR also interacts with structured viral RNAs, and its signaling is modulated by PACT and viral E3.
Conclusions:
- PKR acts as a sensor for both viral and aberrant host RNAs during infection.
- Defective RNA processing, including splicing errors, contributes to PKR activation.
- PKR integrates signals from RNA processing, viral replication, and innate immunity.
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