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Viruses 2018, 10(4), 199; https://doi.org/10.3390/v10040199

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

1
Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina
2
Centro de Virología Animal (CEVAN), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires C1440FFX, Argentina
*
Author to whom correspondence should be addressed.
Received: 29 December 2017 / Revised: 7 April 2018 / Accepted: 9 April 2018 / Published: 17 April 2018
(This article belongs to the Section Animal Viruses)
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Abstract

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. View Full-Text
Keywords: Junín virus; Tacaribe virus; arenavirus; ERK; cell signaling; replication Junín virus; Tacaribe virus; arenavirus; ERK; cell signaling; replication
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Brunetti, J.E.; Foscaldi, S.; Quintana, V.M.; Scolaro, L.A.; López, N.; Castilla, V. Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses. Viruses 2018, 10, 199.

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