scholarly journals Short Interfering RNA Inhibits Rift Valley Fever Virus Replication and Degradation of Protein Kinase R in Human Cells

2016 ◽  
Vol 7 ◽  
Author(s):  
Bonto Faburay ◽  
Juergen A. Richt
Keyword(s):  
Protein Kinase ◽  
Virus Replication ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Human Cells ◽  
Short Interfering Rna ◽  
Protein Kinase R ◽  
Valley Fever ◽  
Interfering Rna

scholarly journals Rift Valley Fever Virus Infection of Human Cells and Insect Hosts Is Promoted by Protein Kinase C Epsilon

PLoS ONE ◽  
2010 ◽  
Vol 5 (11) ◽  
pp. e15483 ◽  
Author(s):  
Claire Marie Filone ◽  
Sheri L. Hanna ◽  
M. Cecilia Caino ◽  
Shelly Bambina ◽  
Robert W. Doms ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Virus Infection ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Human Cells ◽  
Valley Fever ◽  
Kinase C ◽  
Protein Kinase C Epsilon

scholarly journals Curcumin Inhibits Rift Valley Fever Virus Replication in Human Cells

2012 ◽  
Vol 287 (40) ◽  
pp. 33198-33214 ◽  
Author(s):  
Aarthi Narayanan ◽  
Kylene Kehn-Hall ◽  
Svetlana Senina ◽  
Lindsay Lundberg ◽  
Rachel Van Duyne ◽  
...  
Keyword(s):  
Virus Replication ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Human Cells ◽  
Fever Virus ◽  
Valley Fever

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

scholarly journals Curcumin inhibits Rift Valley fever virus replication in human cells.

2014 ◽  
Vol 289 (33) ◽  
pp. 22671-22671
Author(s):  
Aarthi Narayanan ◽  
Kylene Kehn-Hall ◽  
Svetlana Senina ◽  
Lindsay Lundberg ◽  
Rachel Van Duyne ◽  
...  
Keyword(s):  
Virus Replication ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Human Cells ◽  
Fever Virus ◽  
Valley Fever

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 Virion-associated spermidine transmits with Rift Valley fever virus particles to maintain infectivity

2020 ◽  
Author(s):  
Vincent Mastrodomenico ◽  
Jeremy J. Esin ◽  
Shefah Qazi ◽  
Oreoluwa S. Omoba ◽  
Brittany L. Fung ◽  
...  
Keyword(s):  
Virus Replication ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rna Virus ◽  
Rift Valley Fever Virus ◽  
Acid Synthesis ◽  
Fever Virus ◽  
Virus Infectivity ◽  
Cellular Functions ◽  
Valley Fever

AbstractViruses require host cell metabolites to productively infect, and the mechanisms by which viruses usurp these molecules is diverse. One group of cellular metabolites important in virus infection is the polyamines, small positively-charged molecules involved in cell cycle, translation, and nucleic acid synthesis, among other cellular functions. Polyamines also support replication of diverse viruses, and they are important for processes such as transcription, translation, and viral protein enzymatic activity. Rift Valley fever virus (RVFV) is a negative-sense RNA virus that requires polyamines to produce infectious particles. In polyamine depleted conditions, noninfectious particles are produced that interfere with virus replication and stimulate immune signaling. Here, we find that RVFV relies on virion-associated polyamines to maintain infectivity. We show that RVFV replication is facilitated by any of the three biogenic polyamines; however, we specifically find spermidine associated with purified virions. Using a panel of polyamine homologs, we observe that virions can also associate with (R)-3-methylspermidine and norspermidine, though not with other less homologous molecules. Using polyamine reporter cells, we demonstrate that virion-associated polyamines transmit from one infected cell to another. Finally, we find that virions devoid of polyamines are unstable and cannot be supplemented with exogenous polyamines to regain stability or infectivity. These data highlight a unique role for polyamines, and spermidine in particular, in maintaining virus infectivity, a function not previously appreciated. Further, these studies are the first to identify polyamines associated with RVFV virions. Targeting polyamines represents a promising antiviral strategy, and this work highlights a new mechanism by which we can inhibit virus replication through FDA-approved polyamine depleting pharmaceuticals.

scholarly journals Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication

Viruses ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 191 ◽  
Author(s):  
Todd Bell ◽  
Virginia Espina ◽  
Lindsay Lundberg ◽  
Chelsea Pinkham ◽  
Ashwini Brahms ◽  
...  
Keyword(s):  
Virus Replication ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Kinase Inhibitor ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever ◽  
Inhibitor Treatment
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