Activation of protein kinase R is required for induction of stress granules by respiratory syncytial virus but dispensable for viral replication
| Autor: | Michael E. Lindquist, Bernardo A. Mainou, James E. Crowe, Terence S. Dermody |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
RNA viruses
viruses Respiratory Syncytial Virus Infections Biology Cytoplasmic Granules Virus Replication environment and public health Article Virus Cell Line 03 medical and health sciences Stress granule RNA interference eIF-2 kinase Virology Humans 2-Aminopurine 030304 developmental biology 0303 health sciences EIF-2 kinase Respiratory syncytial viruses 030306 microbiology Kinase virus diseases biochemical phenomena metabolism and nutrition Protein kinase R 3. Good health Enzyme Activation enzymes and coenzymes (carbohydrates) Viral replication Cell culture biology.protein Paramyxovirinae |
| Zdroj: | Virology |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2011.02.009 |
| Popis: | We performed experiments to determine the effect of PKR activation on respiratory syncytial virus (RSV) replication. We first determined that RSV infection activates PKR which induces the phosphorylation of eIF2α, resulting in the formation of host stress granules. We used RNA interference to decrease endogenous PKR levels. RSV replication was not altered in cells deficient for PKR expression. However, RSV-mediated stress granule formation was significantly reduced in PKR-knockdown cells. As an alternative method to block PKR activation, we used treatment with the kinase inhibitor 2-aminopurine (2-AP). We observed that 2-AP treatment significantly reduced viral replication. We also treated PKR-knockdown cells with 2-AP and inoculated with RSV. Under these conditions, 2-AP treatment diminished viral replication in the absence of PKR expression. These results suggest that PKR activation has a minimal effect on RSV replication and that the antiviral effect of 2-AP during RSV infection likely occurs via a PKR-independent mechanism. |
| Databáze: | OpenAIRE |
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