Activation of the PKR/eIF2[alpha] signaling cascade inhibits replication of Newcastle disease virus

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. Protei...

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Bibliographic Details
Published in:Virology journal 2014-03, Vol.11 (1), p.62-62
Main Authors: Zhang, Shilei, Sun, Yingjie, Chen, Hongjun, Dai, Yabin, Zhan, Yuan, Yu, Shengqing, Qiu, Xusheng, Tan, Lei, Song, Cuiping, Ding, Chan
Format: Article
Language:English
Subjects:
Development and progression
Genetic aspects
Genomes
Health aspects
Infections
Kinases
Mediation
Newcastle disease
Newcastle disease virus
Phosphorylation
Physiological aspects
Protein kinases
Protein synthesis
Proteins
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Summary: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. NDV infection led to the activation of dsRNA-dependent PKR and phosphorylation of its substrate, translation initiation factor eIF2[alpha], 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 eIF2[alpha] phosphorylation as well as IFN-[beta] mRNA levels, leading to the augmentation of extracellular virus titer. Furthermore, siRNA knockdown or phosphorylation of eIF2[alpha] or okadaic acid treatment significantly impaired NDV replication, indicating the critical role of the PKR/eIF2[alpha] signaling cascade in NDV infection. PKR is activated by dsRNA generated by NDV infection and inhibits NDV replication by eIF2[alpha] phosphorylation. This study provides insight into NDV-host interactions for the development of candidate antiviral strategies.
ISSN:1743-422X
1743-422X
DOI:10.1186/1743-422X-11-62