Year-end Sale % OFF 
Abstract
BackgroundNewcastle 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.ResultsNDV 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.ConclusionPKR 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.
Highlights
Newcastle Disease virus (NDV) causes severe and economically significant disease in almost all birds
NDV infection triggers Protein kinase R (PKR) activation through eIF2α phosphorylation human cervical cancer cell line (HeLa) cells were infected with NDV strain LaSota or Herts/ 33 at a multiplicity of infection (MOI) of 1
Western blot analysis results showed that PKR and eIF2α could be phosphorylated by NDV strains LaSota (Figure 1C) and Herts/33 (Figure 1D) in a dose-dependent manner
Summary
Newcastle Disease virus (NDV) causes severe and economically significant disease in almost all birds. NDV generates long double-stranded RNA (dsRNA) molecules during transcription of single-stranded genomic RNA. Protein kinase R (PKR) is activated by dsRNA. Among the variety of IFN-stimulated gene products, double-stranded RNA-dependent protein kinase (PKR) is a key executor of this antiviral response [2]. As a pattern recognition receptor (PRR) for viral dsRNA, PKR is considered to be significant for type I IFN production [3]. The ubiquitously expressed PKR is usually present in an inactive form at a low abundance, but is activated by conformational change and autophosphorylation upon binding of dsRNA, generated during viral genome replication [4]. As is often the case, for its genomic replication, NDV first generates a full-length positive-strand antigenomic RNA and in turn, serves as a template for the synthesis of new negative-stranded RNA genome, which forms a dsRNA intermediate [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
