Resistance to Vesicular Stomatitis Virus Infection Requires a Functional Cross Talk between the Eukaryotic Translation Initiation Factor 2α Kinases PERK and PKR
| Autor: | Li-Ke Qu, Jaime D. Blais, John C. Bell, Antonis E. Koromilas, Stavroula Papadopoulou, Dionissios Baltzis, Nahum Sonenberg |
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| Rok vydání: | 2004 |
| Předmět: |
endocrine system
viruses Eukaryotic Initiation Factor-2 Immunology Apoptosis Biology Virus Replication Microbiology Vesicular stomatitis Indiana virus Cell Line eIF-2 Kinase Virology Animals Humans Initiation factor Phosphorylation Protein kinase A Caspase 12 EIF-2 kinase eIF2 Kinase biology.organism_classification Protein kinase R Genetic translation Virus-Cell Interactions Cell biology Enzyme Activation Vesicular stomatitis virus Caspases Insect Science biology.protein |
| Zdroj: | Journal of Virology. 78:12747-12761 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.78.23.12747-12761.2004 |
| Popis: | Phosphorylation of the alpha (α) subunit of the eukaryotic translation initiation factor 2 (eIF2) leads to the inhibition of protein synthesis in response to diverse stress conditions, including viral infection. The eIF2α kinase PKR has been shown to play an essential role against vesicular stomatitis virus (VSV) infection. We demonstrate here that another eIF2α kinase, the endoplasmic reticulum-resident protein kinase PERK, contributes to cellular resistance to VSV infection. We demonstrate that mouse embryonic fibroblasts (MEFs) from PERK −/− mice are more susceptible to VSV-mediated apoptosis than PERK +/+ MEFs. The higher replication capacity of VSV in PERK −/− MEFs results from their inability to attenuate viral protein synthesis due to an impaired eIF2α phosphorylation. We also show that VSV-infected PERK −/− MEFs are unable to fully activate PKR, suggesting a cross talk between the two eIF2α kinases in virus-infected cells. These findings further implicate PERK in virus infection, and provide evidence that the antiviral and antiapoptotic roles of PERK are mediated, at least in part, via the activation of PKR. |
| Databáze: | OpenAIRE |
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