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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. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Registro:

Documento: Artículo
Título:Role of the ERK1/2 signaling pathway in the replication of junín and tacaribe viruses
Autor:Brunetti, J.E.; Foscaldi, S.; Quintana, V.M.; Scolaro, L.A.; López, N.; Castilla, V.
Filiación:Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Centro de Virología Animal (CEVAN), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, C1440FFX, Argentina
Palabras clave:Arenavirus; Cell signaling; ERK; Junín virus; Replication; Tacaribe virus; 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene; chlorpromazine; messenger RNA; mitogen activated protein kinase 1; mitogen activated protein kinase 3; ribavirin; small interfering RNA; viral protein; 1,3 butadiene; enzyme inhibitor; nitrile; viral protein; virus RNA; animal cell; Article; cell proliferation; cell viability; controlled study; gene expression; genetic transfection; immunofluorescence test; Junin virus; nonhuman; phosphorylation; protein expression; real time polymerase chain reaction; reverse transcription polymerase chain reaction; signal transduction; Tacaribe virus; virus entry; virus infectivity; virus replication; Western blotting; animal; biosynthesis; cell line; host pathogen interaction; MAPK signaling; metabolism; New World arenavirus; physiology; Animals; Arenaviruses, New World; Butadienes; Cell Line; Enzyme Inhibitors; Host-Pathogen Interactions; MAP Kinase Signaling System; Nitriles; RNA, Viral; Viral Proteins; Virus Replication
Año:2018
Volumen:10
Número:4
DOI: http://dx.doi.org/10.3390/v10040199
Título revista:Viruses
Título revista abreviado:Viruses
ISSN:19994915
CAS:1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene, 109511-58-2; chlorpromazine, 50-53-3, 69-09-0; mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6; ribavirin, 36791-04-5; 1,3 butadiene, 106-99-0, 25339-57-5; Butadienes; Enzyme Inhibitors; Nitriles; RNA, Viral; U 0126; Viral Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19994915_v10_n4_p_Brunetti

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Citas:

---------- APA ----------
Brunetti, J.E., Foscaldi, S., Quintana, V.M., Scolaro, L.A., López, N. & Castilla, V. (2018) . Role of the ERK1/2 signaling pathway in the replication of junín and tacaribe viruses. Viruses, 10(4).
http://dx.doi.org/10.3390/v10040199
---------- CHICAGO ----------
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 10, no. 4 (2018).
http://dx.doi.org/10.3390/v10040199
---------- MLA ----------
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, vol. 10, no. 4, 2018.
http://dx.doi.org/10.3390/v10040199
---------- VANCOUVER ----------
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(4).
http://dx.doi.org/10.3390/v10040199