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

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...

Full description

Saved in:
Bibliographic Details
Published in:Virology journal 2014-03, Vol.11 (1), p.62-62, Article 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:
acid treatment
Animals
Birds
Cell Line
dose response
double-stranded RNA
eIF-2 Kinase - metabolism
Eukaryotic Initiation Factor-2 - metabolism
Humans
interferon-beta
messenger RNA
Newcastle disease virus
Newcastle disease virus - immunology
Newcastle disease virus - physiology
okadaic acid
phosphorylation
protein kinases
RNA, Double-Stranded - immunology
RNA, Viral - immunology
Signal Transduction
small interfering RNA
viral load
Virus Replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1743-422X
1743-422X
DOI:10.1186/1743-422X-11-62