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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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Autores principales: Brunetti, Jesús E., Foscaldi, Sabrina, Quintana, Verónica M., Scolaro, Luis A., López, Nora, Castilla, Viviana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923493/
https://www.ncbi.nlm.nih.gov/pubmed/29673133
http://dx.doi.org/10.3390/v10040199
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author Brunetti, Jesús E.
Foscaldi, Sabrina
Quintana, Verónica M.
Scolaro, Luis A.
López, Nora
Castilla, Viviana
author_facet Brunetti, Jesús E.
Foscaldi, Sabrina
Quintana, Verónica M.
Scolaro, Luis A.
López, Nora
Castilla, Viviana
author_sort Brunetti, Jesús E.
collection PubMed
description 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.
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spelling pubmed-59234932018-05-03 Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses Brunetti, Jesús E. Foscaldi, Sabrina Quintana, Verónica M. Scolaro, Luis A. López, Nora Castilla, Viviana Viruses Article 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. MDPI 2018-04-17 /pmc/articles/PMC5923493/ /pubmed/29673133 http://dx.doi.org/10.3390/v10040199 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brunetti, Jesús E.
Foscaldi, Sabrina
Quintana, Verónica M.
Scolaro, Luis A.
López, Nora
Castilla, Viviana
Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses
title Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses
title_full Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses
title_fullStr Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses
title_full_unstemmed Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses
title_short Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses
title_sort role of the erk1/2 signaling pathway in the replication of junín and tacaribe viruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923493/
https://www.ncbi.nlm.nih.gov/pubmed/29673133
http://dx.doi.org/10.3390/v10040199
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