ZIKV Strains Elicit Different Inflammatory and Anti-Viral Responses in Microglia Cells
Fernanda Bellaniza Caminha de Oliveira,
Vanessa Paola Alves Sampaio de Sá Freire,
Sharton Vinicius Antunes Coelho,
Lana Monteiro Meuren,
Julys da Fonseca Palmeira,
Ana Luísa Cardoso,
Francisco de Assis Rocha Neves,
Bergmann Morais Ribeiro,
Gustavo Adolfo Argañaraz,
Luciana Barros de Arruda,
Enrique Roberto Argañaraz
Affiliations
Fernanda Bellaniza Caminha de Oliveira
Laboratory of Molecular Neurovirology, Department of Pharmacy, Faculty of Health Science, University of Brasília, Brasília 70910-900, DF, Brazil
Vanessa Paola Alves Sampaio de Sá Freire
Laboratory of Molecular Neurovirology, Department of Pharmacy, Faculty of Health Science, University of Brasília, Brasília 70910-900, DF, Brazil
Sharton Vinicius Antunes Coelho
Laboratório de Genética e Imunologia das Infecções Virais, Departamento de Virologia, Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
Lana Monteiro Meuren
Laboratório de Genética e Imunologia das Infecções Virais, Departamento de Virologia, Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
Julys da Fonseca Palmeira
Laboratory of Molecular Neurovirology, Department of Pharmacy, Faculty of Health Science, University of Brasília, Brasília 70910-900, DF, Brazil
Ana Luísa Cardoso
Centre for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
Francisco de Assis Rocha Neves
Laboratory of Molecular Pharmacology, Faculty of Health Science, University of Brasília, Brasilia 70910-900, DF, Brazil
Bergmann Morais Ribeiro
Laboratory of Bacuolovirus, Cell Biology Department, University of Brasilia, Brasilia 70910-900, DF, Brazil
Gustavo Adolfo Argañaraz
Laboratory of Molecular Neurovirology, Department of Pharmacy, Faculty of Health Science, University of Brasília, Brasília 70910-900, DF, Brazil
Luciana Barros de Arruda
Laboratório de Genética e Imunologia das Infecções Virais, Departamento de Virologia, Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
Enrique Roberto Argañaraz
Laboratory of Molecular Neurovirology, Department of Pharmacy, Faculty of Health Science, University of Brasília, Brasília 70910-900, DF, Brazil
In recent years, the Zika Virus (ZIKV) has caused pandemic outbreaks associated with a high rate of congenital ZIKV syndrome (CZS). Although all strains associated with worldwide outbreaks derive from the Asian lineage, the reasons for their enhanced spread and severity are not fully understood. In this study, we conducted a comparative analysis of miRNAs (miRNA-155/146a/124) and their cellular targets (SOCS1/3, SHP1, TRAF6, IRAK1), as well as pro- and anti-inflammatory and anti-viral cytokines (IL-6, TNF-α, IFN-γ, IL-10, and IFN-β) and peroxisome proliferator-activated receptor γ (PPAR-γ) expression in BV2 microglia cells infected with ZIKV strains derived from African and Asian lineages (ZIKVMR766 and ZIKVPE243). BV2 cells were susceptible to both ZIKV strains, and showed discrete levels of viral replication, with delayed release of viral particles without inducing significant cytopathogenic effects. However, the ZIKVMR766 strain showed higher infectivity and replicative capacity, inducing a higher expression of microglial activation markers than the ZIKVPE243 strain. Moreover, infection with the ZIKVMR766 strain promoted both a higher inflammatory response and a lower expression of anti-viral factors compared to the ZIKVPE243 strain. Remarkably, the ZIKKPE243 strain induced significantly higher levels of the anti-inflammatory nuclear receptor—PPAR-γ. These findings improve our understanding of ZIKV-mediated modulation of inflammatory and anti-viral innate immune responses and open a new avenue to explore underlining mechanisms involved in the pathogenesis of ZIKV-associated diseases.
