Double-Stranded RNA Deaminase ADAR1 Increases Host Susceptibility to Virus Infection
| Autor: | Jing-Hua Yang, Graeme L. Hammond, Yongzhan Nie |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adenosine Deaminase
viruses Eukaryotic Initiation Factor-2 Immunology Cellular Response to Infection Microbiology Vesicular stomatitis Indiana virus Cell Line Mice eIF-2 Kinase RNA interference Virology Animals Humans Phosphorylation Kinase activity RNA Double-Stranded EIF-2 kinase biology RNA-Binding Proteins RNA biology.organism_classification Protein kinase R Enzyme Activation RNA silencing Viral replication Vesicular stomatitis virus Insect Science NIH 3T3 Cells biology.protein RNA Viral |
| Zdroj: | Journal of Virology. 81:917-923 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | The RNA-editing enzyme ADAR1 is a double-stranded RNA (dsRNA) binding protein that modifies cellular and viral RNA sequences by adenosine deamination. ADAR1 has been demonstrated to play important roles in embryonic erythropoiesis, viral response, and RNA interference. In human hepatitis virus infection, ADAR1 has been shown to target viral RNA and to suppress viral replication through dsRNA editing. It is not clear whether this antiviral effect of ADAR1 is a common mechanism in response to viral infection. Here, we report a proviral effect of ADAR1 that enhances replication of vesicular stomatitis virus (VSV) through a mechanism independent of dsRNA editing. We demonstrate that ADAR1 interacts with dsRNA-activated protein kinase PKR, inhibits its kinase activity, and suppresses the α subunit of eukaryotic initiation factor 2 (eIF-2α) phosphorylation. Consistent with the inhibitory effect on PKR activation, ADAR1 increases VSV infection in PKR +/+ mouse embryonic fibroblasts; however, no significant effect was found in PKR −/− cells. This proviral effect of ADAR1 requires the N-terminal domains but does not require the deaminase domain. These findings reveal a novel mechanism of ADAR1 that increases host susceptibility to viral infection by inhibiting PKR activation. |
| Databáze: | OpenAIRE |
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