title: Activation of the PKR/eIF2α signaling cascade inhibits replication of Newcastle disease virus.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Shilei
authors.initials: S
authors.lastname: Zhang
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Sun
authors.forename: Hongjun
authors.initials: H
authors.lastname: Chen
authors.forename: Yabin
authors.initials: Y
authors.lastname: Dai
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Shengqing
authors.initials: S
authors.lastname: Yu
authors.forename: Xusheng
authors.initials: X
authors.lastname: Qiu
authors.forename: Lei
authors.initials: L
authors.lastname: Tan
authors.forename: Cuiping
authors.initials: C
authors.lastname: Song
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No,518 Ziyue Road, Shanghai 200241, China. shoveldeen@shvri.ac.cn.
authors.forename: Chan
authors.initials: C
authors.lastname: Ding
mesh_terms: D000818:Animals; D001717:Birds; D002460:Cell Line; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D006801:Humans; D009522:Newcastle disease virus / Q000276:immunology* / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology; D015398:Signal Transduction; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D019892:eIF-2 Kinase