Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses

We have previously shown that the infection of cell cultures with the arenaviruses Junín (JUNV), Tacaribe (TCRV), and Pichindé promotes the phosphorylation of mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases 1 and 2 (ERK1/2) and that this activation is required for th...

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Bibliographic Details
Published in:Viruses 2018-04, Vol.10 (4), p.199
Main Authors: Brunetti, Jesús E, Foscaldi, Sabrina, Quintana, Verónica M, Scolaro, Luis A, López, Nora, Castilla, Viviana
Format: Article
Language:English
Subjects:
Antibodies
arenavirus
cell signaling
ERK
Extracellular signal-regulated kinase
Gene expression
Genomes
Infections
Infectious diseases
Internalization
Junín virus
Kinases
Macromolecules
mRNA
Phosphorylation
Plasmids
Protein biosynthesis
Protein kinase
Proteins
replication
Reporter gene
RNA polymerase
Signal transduction
Tacaribe virus
Transcription
Translation
Uncoating
Vaccines
Viral infections
Viruses
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Summary:We have previously shown that the infection of cell cultures with the arenaviruses Junín (JUNV), Tacaribe (TCRV), and Pichindé promotes the phosphorylation of mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases 1 and 2 (ERK1/2) and that this activation is required for the achievement of a productive infection. Here we examined the contribution of ERK1/2 in early steps of JUNV and TCRV multiplication. JUNV adsorption, internalization, and uncoating were not affected by treatment of cultured cells with U0126, an inhibitor of the ERK1/2 signaling pathway. In contrast, U0126 caused a marked reduction in viral protein expression and RNA synthesis, while JUNV RNA synthesis was significantly augmented in the presence of an activator of the ERK1/2 pathway. Moreover, U0126 impaired the expression of a reporter gene in a TCRV-based replicon system, confirming the ability of the compound to hinder arenavirus macromolecular synthesis. By using a cell-based assay, we determined that the inhibitor did not affect the translation of a synthetic TCRV-like mRNA. No changes in the phosphorylation pattern of the translation factor eIF2α were found in U0126-treated cells. Our results indicate that U0126 impairs viral RNA synthesis, thereby leading to a subsequent reduction in viral protein expression. Thus, we conclude that ERK1/2 signaling activation is required for an efficient arenavirus RNA synthesis.
ISSN:1999-4915
1999-4915
DOI:10.3390/v10040199