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 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 NSs Protein of Rift Valley Fever Virus Induces the Specific Degradation of the Double-Stranded RNA-Dependent Protein Kinase

2009 ◽  
Vol 83 (9) ◽  
pp. 4365-4375 ◽  
Author(s):  
Matthias Habjan ◽  
Andreas Pichlmair ◽  
Richard M. Elliott ◽  
Anna K. Överby ◽  
Timo Glatter ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Wild Type ◽  
Dependent Protein Kinase ◽  
Valley Fever ◽  
Double Stranded Rna ◽  
Dependent Protein ◽  
Specific Degradation

ABSTRACT Rift Valley fever virus (RVFV) continues to cause large outbreaks of acute febrile and often fatal illness among humans and domesticated animals in Africa, Saudi Arabia, and Yemen. The high pathogenicity of this bunyavirus is mainly due to the viral protein NSs, which was shown to prevent transcriptional induction of the antivirally active type I interferons (alpha/beta interferon [IFN-α/β]). Viruses lacking the NSs gene induce synthesis of IFNs and are therefore attenuated, whereas the noninducing wild-type RVFV strains can only be inhibited by pretreatment with IFN. We demonstrate here in vitro and in vivo that a substantial part of the antiviral activity of IFN against RVFV is due to a double-stranded RNA-dependent protein kinase (PKR). PKR-mediated virus inhibition, however, was much more pronounced for the strain Clone 13 with NSs deleted than for the NSs-expressing strain ZH548. In vivo, Clone 13 was nonpathogenic for wild-type (wt) mice but could regain pathogenicity if mice lacked the PKR gene. ZH548, in contrast, killed both wt and PKR knockout mice indiscriminately. ZH548 was largely resistant to the antiviral properties of PKR because RVFV NSs triggered the specific degradation of PKR via the proteasome. The NSs proteins of the related but less virulent sandfly fever Sicilian virus and La Crosse virus, in contrast, had no such anti-PKR activity despite being efficient suppressors of IFN induction. Our data suggest that RVFV NSs has gained an additional anti-IFN function that may explain the extraordinary pathogenicity of this virus.

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
Sign in / Sign up

Export Citation Format

Share Document