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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
ZIKV Strains Elicit Different Inflammatory and Anti-Viral Responses in Microglia Cells
Fernanda Bellaniza Caminha de Oliveira1, Vanessa Paola Alves Sampaio de Sá Freire1, Sharton Vinicius Antunes Coelho2
1Laboratory of Molecular Neurovirology, Department of Pharmacy, Faculty of Health Science, University of Brasília, Brasília 70910-900, DF, Brazil.
Abstract:
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.
Insights
The African Zika Virus (ZIKV) strain (ZIKVMR766) showed higher infectivity and inflammatory response in microglia cells compared to the Asian strain (ZIKVPE243). The Asian strain induced higher anti-inflammatory PPAR-γ levels, offering insights into ZIKV pathogenesis.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Zika Virus (ZIKV) outbreaks, particularly those linked to congenital ZIKV syndrome (CZS), predominantly involve the Asian lineage.
- The underlying factors contributing to the increased spread and severity of Asian ZIKV strains remain incompletely understood.
Purpose of the Study:
- To comparatively analyze the immune response in BV2 microglia cells infected with African (ZIKVMR766) and Asian (ZIKVPE243) ZIKV strains.
- To investigate the differential expression of microRNAs, their targets, inflammatory cytokines, antiviral factors, and PPAR-γ.
Main Methods:
- BV2 microglia cells were infected with ZIKVMR766 (African) and ZIKVPE243 (Asian) strains.
- Analysis included viral replication, microglial activation markers, pro- and anti-inflammatory cytokines (IL-6, TNF-α, IFN-γ, IL-10, IFN-β), antiviral factors, and peroxisome proliferator-activated receptor γ (PPAR-γ).
- Expression levels of specific microRNAs (miRNA-155/146a/124) and their targets (SOCS1/3, SHP1, TRAF6, IRAK1) were assessed.
Main Results:
- Both ZIKV strains infected BV2 cells, with the African ZIKVMR766 strain exhibiting higher infectivity and replication.
- ZIKVMR766 induced greater microglial activation, a stronger inflammatory response, and lower antiviral factor expression compared to ZIKVPE243.
- The Asian ZIKVPE243 strain significantly upregulated the anti-inflammatory nuclear receptor PPAR-γ.
Conclusions:
- ZIKV strain lineage influences the modulation of innate immune responses in microglia.
- The African ZIKV strain elicits a more pronounced inflammatory response, while the Asian strain promotes higher anti-inflammatory signaling via PPAR-γ.
- These findings contribute to understanding ZIKV pathogenesis and host-pathogen interactions in ZIKV-associated diseases.
