Robust antiviral innate immune response and miRNA regulatory network were identified in ZIKV-infected cells: implications in the pathogenesis of ZIKV infection.

Abstract

Zika virus (ZIKV) infection has emerged as a significant public health concern due to its association with fetal microcephaly and Guillain-Barre syndrome (GBS). Unfortunately, its detailed pathogenesis remains unclear. To better understand how ZIKV evades host antiviral immunity, we analyzed the microarray dataset (GSE98889) of ZIKV-infected primary human brain microvascular endothelial cells (hBMECs) retrieved from the gene expression omnibus (GEO). 160, 1423, 969, 829, and 600 differentially expressed genes (DEGs) were identified at 12, 24, 48, 72, and 216 hours post-ZIKV infection in hBMECs, respectively. Subsequently, 31 common DEGs across all time-points were selected for further analysis. Gene ontology (GO) functional analysis showed these 31 DEGs were mainly involved in the host antiviral innate immune responses. Protein-protein interaction (PPI) network analysis identified 10 hub genes (MX1, OAS1, OAS2, IFI44, IFI44L, IFIT1, IFIT2, IFIT3, IFIH1, and XAF1), which were all interferon-stimulated genes (ISGs) and upregulated. qRT-PCR was used to validate the expression patterns of these 10 hub genes in different ZIKV-infected cell lines. Finally, miRNA-mRNA regulatory network analysis revealed that hsa-miR-129-2-3p, hsa-miR-138-5p, hsa-miR-21-3p, hsa-miR-27a-5p, hsa-miR-449a, and hsa-miR449b-5p were key miRNAs regulating these hub genes. Our study showed that ZIKV infection activated the host innate immune response to restrict ZIKV infection. The common pathways, hub genes, and their regulatory miRNA network offer new insights into virus-host interactions, enhancing our understanding of ZIKV pathogenesis.