scholarly journals Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2α Phosphorylation

2009 ◽  
Vol 5 (2) ◽  
pp. e1000287 ◽  
Author(s):  
Tetsuro Ikegami ◽  
Krishna Narayanan ◽  
Sungyong Won ◽  
Wataru Kamitani ◽  
C. J. Peters ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever ◽  
Eif2α Phosphorylation

scholarly journals NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR

2016 ◽  
Vol 90 (13) ◽  
pp. 6140-6147 ◽  
Author(s):  
Markus Kainulainen ◽  
Simone Lau ◽  
Charles E. Samuel ◽  
Veit Hornung ◽  
Friedemann Weber
Keyword(s):  
Protein Kinase ◽  
Host Cell ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Substrate Recognition ◽  
Fever Virus ◽  
Valley Fever ◽  
Content Type ◽  
F Box Protein

ABSTRACTRift Valley fever virus (RVFV, familyBunyaviridae, genusPhlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells.IMPORTANCERift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we demonstrate that NSs requires E3 ubiquitin ligase complexes of the SCF (Skp1, Cul1, F-box protein) type to destroy PKR. SCF-type complexes can engage variant ubiquitination substrate recognition subunits, and we found the F-box proteins FBXW11 and β-TRCP1 to be relevant for the action of NSs against PKR. Thus, we identified the host cell factors that are critically needed by Rift Valley fever virus to uphold its replication against the potent antiviral kinase PKR.

scholarly journals Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR

Virology ◽  
2013 ◽  
Vol 435 (2) ◽  
pp. 415-424 ◽  
Author(s):  
Birte Kalveram ◽  
Olga Lihoradova ◽  
Sabarish V. Indran ◽  
Nandadeva Lokugamage ◽  
Jennifer A. Head ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Dependent Protein Kinase ◽  
Valley Fever ◽  
Dependent Protein

scholarly journals Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase

2016 ◽  
Vol 12 (2) ◽  
pp. e1005437 ◽  
Author(s):  
Rajini Mudhasani ◽  
Julie P. Tran ◽  
Cary Retterer ◽  
Krishna P. Kota ◽  
Chris A. Whitehouse ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Virus Infection ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
E3 Ligase ◽  
Fever Virus ◽  
Protein Kinase R ◽  
Valley Fever

Complement fixation reaction of Rift Valley fever virus

1950 ◽  
Vol 5 (5) ◽  
pp. 243-247
Author(s):  
Minoru MATSUMOTO ◽  
Saburo IWASA ◽  
Motosige ENDO
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Complement Fixation ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever ◽  
Fixation Reaction
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