scholarly journals The NS5A/NS5 Proteins of Viruses from Three Genera of the Family Flaviviridae Are Phosphorylated by Associated Serine/Threonine Kinases

1998 ◽  
Vol 72 (7) ◽  
pp. 6199-6206 ◽  
Author(s):  
Karen E. Reed ◽  
Alexander E. Gorbalenya ◽  
Charles M. Rice
Keyword(s):  
Mammalian Cells ◽  
Yellow Fever Virus ◽  
Diarrhea Virus ◽  
The Family ◽  
A Cell ◽  
Infected Cells ◽  
Threonine Kinases ◽  
The One ◽  
Viral Diarrhea Virus

ABSTRACT Phosphorylation of the expressed NS5A protein of hepatitis C virus (HCV), a member of the Hepacivirus genus of the familyFlaviviridae, has been demonstrated in mammalian cells and in a cell-free assay by an associated kinase activity. In this report, phosphorylation is also shown for the NS5A and NS5 proteins, respectively, of bovine viral diarrhea virus (BVDV) and yellow fever virus (YF), members of the other two established genera in this family. Phosphorylation of BVDV NS5A and YF NS5 was observed in infected cells, transient expression experiments, and a cell-free assay similar to the one developed for HCV NS5A. Phosphoamino acid analyses indicated that all three proteins were phosphorylated by serine/threonine kinases. Similarities in the properties of BVDV NS5A, YF NS5, and HCV NS5A phosphorylation in vitro further suggested that closely related kinases or the same kinase may phosphorylate these viral proteins. Conservation of this trait among three quite distantly related viruses representing three separate genera suggests that phosphorylation of the NS5A/NS5 proteins or their association with cellular kinases may play an important role in the flavivirus life cycle.

scholarly journals RNase-dependent inhibition of extracellular, but not intracellular, dsRNA-induced interferon synthesis by Erns of pestiviruses

2008 ◽  
Vol 89 (10) ◽  
pp. 2501-2506 ◽  
Author(s):  
Ioannis Magkouras ◽  
Philippe Mätzener ◽  
Till Rümenapf ◽  
Ernst Peterhans ◽  
Matthias Schweizer
Keyword(s):  
Mammalian Cells ◽  
Host Population ◽  
Glycoprotein E ◽  
Diarrhea Virus ◽  
Dependent Inhibition ◽  
Order Of Magnitude ◽  
Infected Cells ◽  
Viral Diarrhea Virus ◽  
Intracellular Dsrna

Recombinant pestivirus envelope glycoprotein Erns has been shown to interfere with dsRNA-induced interferon (IFN-α/β) synthesis. This study demonstrated that authentic, enzymically active Erns produced in mammalian cells prevented a dsRNA-induced IFN response when present in the supernatant of bovine cells. Strikingly, IFN synthesis of cells expressing Erns was eliminated after extracellular addition, but not transfection, of dsRNA. Importantly, the same applied to cells infected with bovine viral diarrhea virus (BVDV) expressing Erns but lacking the N-terminal protease Npro. Free Erns concentrations circulating in the blood of animals persistently infected with BVDV were determined to be approximately 50 ng ml−1, i.e. at a similar order of magnitude as that displaying an effect on dsRNA-induced IFN expression in vitro. Whilst Npro blocks interferon regulatory factor-3-dependent IFN induction in infected cells, Erns may prevent constant IFN induction in uninfected cells by dsRNA that could originate from pestivirus-infected cells. This probably contributes to the survival of persistently BVDV-infected animals and maintains viral persistence in the host population.

scholarly journals Synergistic In Vitro Interactions between Alpha Interferon and Ribavirin against Bovine Viral Diarrhea Virus and Yellow Fever Virus as Surrogate Models of Hepatitis C Virus Replication

2003 ◽  
Vol 47 (7) ◽  
pp. 2293-2298 ◽  
Author(s):  
Victor E. Buckwold ◽  
Jiayi Wei ◽  
Michelle Wenzel-Mathers ◽  
Julie Russell
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Yellow Fever ◽  
Bovine Viral Diarrhea Virus ◽  
Yellow Fever Virus ◽  
Bovine Viral Diarrhea ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Viral Diarrhea Virus

ABSTRACT Monotherapy of hepatitis C virus infection with either alpha interferon or ribavirin alone is rather ineffective, while the use of the two antivirals together is much more efficacious. In vitro drug-drug combination analysis utilizing related members of the family Flaviviridae, bovine viral diarrhea virus and yellow fever virus, revealed significant direct synergistic interactions between these drugs' antiviral activities that might explain this clinical observation.

scholarly journals Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 244
Author(s):  
Laura Albentosa-González ◽  
Rosario Sabariegos ◽  
Armando Arias ◽  
Pilar Clemente-Casares ◽  
Antonio Mas
Keyword(s):  
Public Health ◽  
Confocal Microscopy ◽  
Viral Replication ◽  
Insufficient Data ◽  
Health Concerns ◽  
Usutu Virus ◽  
A Cell ◽  
Infected Cells ◽  
Specific Inhibitors

Usutu virus (USUV) is a flavivirus that mainly infects wild birds through the bite of Culex mosquitoes. Recent outbreaks have been associated with an increased number of cases in humans. Despite being a growing source of public health concerns, there is yet insufficient data on the virus or host cell targets for infection control. In this work we have investigated whether the cellular kinase Akt and USUV polymerase NS5 interact and co-localize in a cell. To this aim, we performed co-immunoprecipitation (Co-IP) assays, followed by confocal microscopy analyses. We further tested whether NS5 is a phosphorylation substrate of Akt in vitro. Finally, to examine its role in viral replication, we chemically silenced Akt with three inhibitors (MK-2206, honokiol and ipatasertib). We found that both proteins are localized (confocal) and pulled down (Co-IP) together when expressed in different cell lines, supporting the fact that they are interacting partners. This possibility was further sustained by data showing that NS5 is phosphorylated by Akt. Treatment of USUV-infected cells with Akt-specific inhibitors led to decreases in virus titers (>10-fold). Our results suggest an important role for Akt in virus replication and stimulate further investigations to examine the PI3K/Akt/mTOR pathway as an antiviral target.

scholarly journals Alpha/Beta and Gamma Interferons Are Induced by Infection with Noncytopathic Bovine Viral Diarrhea Virus In Vivo

2002 ◽  
Vol 76 (2) ◽  
pp. 923-927 ◽  
Author(s):  
B. Charleston ◽  
L. S. Brackenbury ◽  
B. V. Carr ◽  
M. D. Fray ◽  
J. C. Hope ◽  
...  
Keyword(s):  
Bovine Viral Diarrhea Virus ◽  
Transforming Growth Factor ◽  
Bovine Viral Diarrhea ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Alpha Beta ◽  
Interferon Responses ◽  
Viral Diarrhea Virus

ABSTRACT In contrast to the results of previous in vitro studies, experimental infection of calves with noncytopathic bovine viral diarrhea virus (ncpBVDV) was found to induce strong alpha/beta and gamma interferon responses in gnotobiotic animals. These responses were associated with depressed levels of transforming growth factor β (TGF-β) in serum. The results of this study indicate that the immunosuppression caused by ncpBVDV is not associated with low interferon responses or elevated levels of TGF-β.

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