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Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR
- Source :
- Virology. 435(2):415-424
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general transcription including IFN-β gene inhibition. MP-12 NSs but not R173A NSs binds to wt PKR. R173A NSs formed filamentous structure in nucleus in a mosaic pattern, which was distinct from MP-12 NSs filament pattern. Due to early phosphorylation of eIF2α, rMP12-NSsR173A could not efficiently accumulate viral proteins. Our results suggest that NSs-mediated host general transcription suppression occurs independently of PKR degradation, while the PKR degradation is important to inhibit the phosphorylation of eIF2α in infected cells undergoing host general transcription suppression.
- Subjects :
- viruses
Mutant
Eukaryotic Initiation Factor-2
Viral Nonstructural Proteins
Virus Replication
environment and public health
Article
Cell Line
Mice
Viral Proteins
eIF-2 Kinase
Transcription (biology)
Interferon
Virology
Chlorocebus aethiops
medicine
Animals
Humans
Phosphorylation
Protein kinase A
Vero Cells
RNA, Double-Stranded
EIF-2 kinase
biology
NSs protein
PKR
Fibroblasts
Rift Valley fever virus
Protein kinase R
Molecular biology
enzymes and coenzymes (carbohydrates)
HEK293 Cells
MP-12
Viral replication
Reverse genetics
Mutation
biology.protein
Bunyavirus
medicine.drug
Subjects
Details
- ISSN :
- 00426822
- Volume :
- 435
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Virology
- Accession number :
- edsair.doi.dedup.....6d0d4842168c69e7a7d6c47be6a0a54f
- Full Text :
- https://doi.org/10.1016/j.virol.2012.09.031