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Article

Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

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Grupo de Biología Celular y Molecular de Arbovirus, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panamá 0816-02593, Panama
2
Programa de Maestría en Microbiología Ambiental, Universidad de Panamá, Panamá 0824, Panama
3
Programa de Doctorado en Ciencias Biológicas, Universidad de la República, Montevideo 11200, Uruguay
*
Author to whom correspondence should be addressed.
Academic Editor: Remi N. Charrel
Viruses 2021, 13(6), 1156; https://doi.org/10.3390/v13061156
Received: 24 April 2021 / Revised: 31 May 2021 / Accepted: 12 June 2021 / Published: 17 June 2021
(This article belongs to the Collection Emerging Arboviruses, Volume II)
Mayaro virus (MAYV) hijacks the host’s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPK inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126, or Losmapimod were quantified using plaque assay. Additionally, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection. View Full-Text
Keywords: Mayaro; MAPKs; p38; SB203580; PROTACs; NR-7; Losmapimod; replication; inhibition Mayaro; MAPKs; p38; SB203580; PROTACs; NR-7; Losmapimod; replication; inhibition
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MDPI and ACS Style

Sugasti-Salazar, M.; Llamas-González, Y.Y.; Campos, D.; González-Santamaría, J. Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells. Viruses 2021, 13, 1156. https://doi.org/10.3390/v13061156

AMA Style

Sugasti-Salazar M, Llamas-González YY, Campos D, González-Santamaría J. Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells. Viruses. 2021; 13(6):1156. https://doi.org/10.3390/v13061156

Chicago/Turabian Style

Sugasti-Salazar, Madelaine, Yessica Y. Llamas-González, Dalkiria Campos, and José González-Santamaría. 2021. "Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells" Viruses 13, no. 6: 1156. https://doi.org/10.3390/v13061156

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