Downregulation of Microcephaly-Causing Genes as a Mechanism for ZIKV Teratogenesis: A Meta-analysis of RNA-Seq Studies.

Abstract

Zika virus (ZIKV) is a neurotropic teratogen that causes congenital Zika syndrome (CZS), characterized by brain and eye anomalies. Impaired gene expression in neural cells after ZIKV infection has been demonstrated; however, there is a gap in the literature of studies comparing whether the differentially expressed genes in such cells are similar and how it can cause CZS. Therefore, the aim of this study was to compare the differential gene expression (DGE) after ZIKV infection in neural cells through a meta-analysis approach. Through the GEO database, studies that evaluated DGE in cells exposed to the Asian lineage of ZIKV versus cells, of the same type, not exposed were searched. From the 119 studies found, five meet our inclusion criteria. Raw data of them were retrieved, pre-processed, and evaluated. The meta-analysis was carried out by comparing seven datasets, from these five studies. We found 125 upregulated genes in neural cells, mainly interferon-stimulated genes, such as IFI6, ISG15, and OAS2, involved in the antiviral response. Furthermore, 167 downregulated, involved with cellular division. Among these downregulated genes, classic microcephaly-causing genes stood out, such as CENPJ, ASPM, CENPE, and CEP152, demonstrating a possible mechanism by which ZIKV impairs brain development and causes CZS.