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Activation of the PKR/eIF2α signaling cascade inhibits replication of Newcastle disease virus
- Source :
- Virology Journal
- Publication Year :
- 2013
-
Abstract
- Background Newcastle Disease virus (NDV) causes severe and economically significant disease in almost all birds. However, factors that affect NDV replication in host cells are poorly understood. NDV generates long double-stranded RNA (dsRNA) molecules during transcription of single-stranded genomic RNA. Protein kinase R (PKR) is activated by dsRNA. The aim of this study was to elucidate the role of PKR in NDV infection. Results NDV infection led to the activation of dsRNA-dependent PKR and phosphorylation of its substrate, translation initiation factor eIF2α, in a dose-dependent manner by either the lentogenic strain LaSota or a velogenic strain Herts/33. PKR activation coincided with the accumulation of dsRNA induced by NDV infection. PKR knockdown remarkably decreased eIF2α phosphorylation as well as IFN-β mRNA levels, leading to the augmentation of extracellular virus titer. Furthermore, siRNA knockdown or phosphorylation of eIF2α or okadaic acid treatment significantly impaired NDV replication, indicating the critical role of the PKR/eIF2α signaling cascade in NDV infection. Conclusion PKR is activated by dsRNA generated by NDV infection and inhibits NDV replication by eIF2α phosphorylation. This study provides insight into NDV-host interactions for the development of candidate antiviral strategies.
- Subjects :
- animal structures
animal diseases
viruses
Eukaryotic Initiation Factor-2
Newcastle disease virus
eIF2α
dsRNA
Biology
Virus Replication
Virus
Cell Line
Birds
eIF-2 Kinase
Transcription (biology)
Virology
Animals
Humans
HeLa cells
RNA, Double-Stranded
Gene knockdown
EIF-2 kinase
Research
PKR
biochemical phenomena, metabolism, and nutrition
Protein kinase R
RNA silencing
Infectious Diseases
Viral replication
embryonic structures
biology.protein
Phosphorylation
RNA, Viral
Signal Transduction
Subjects
Details
- ISSN :
- 1743422X
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Virology journal
- Accession number :
- edsair.doi.dedup.....3ca1362766b16a1b485d27f0fdd96452