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Open Access Highly Accessed Research

Activation of the PKR/eIF2α signaling cascade inhibits replication of Newcastle disease virus

Shilei Zhang1, Yingjie Sun1, Hongjun Chen1, Yabin Dai2, Yuan Zhan1, Shengqing Yu1, Xusheng Qiu1, Lei Tan1, Cuiping Song1 and Chan Ding1*

Author Affiliations

1 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No.518 Ziyue Road, Shanghai 200241, China

2 Poultry Institute, Chinese Academy of Agricultural Sciences, Yangzhou, Jiangsu 225125, China

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Virology Journal 2014, 11:62  doi:10.1186/1743-422X-11-62

Published: 31 March 2014

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.

Keywords:
Newcastle disease virus; dsRNA; PKR; eIF2α; HeLa cells