In vitro zika virus infection of human neural progenitor cells: Meta-analysis of RNA-seq assays

Rossella Gratton, Paola Maura Tricarico, Almerinda Agrelli, Heverton Valentim Colaço da Silva, Lucas Coêlho Bernardo, Sergio Crovella, Antonio Victor Campos Coelho, Ronald Rodrigues de Moura, Lucas André Cavalcanti Brandão

Research output: Contribution to journalReview articlepeer-review

Abstract

The Zika virus (ZIKV) is an emergent arthropod-borne virus (arbovirus) responsible for congenital Zika syndrome (CZS) and a range of other congenital malformations. Evidence shows that ZIKV infects human neural progenitor cells (hNPCs) in the fetal brain, prompting inflammation and tissue damage/loss. Despite recent advances, little is known about the pathways involved in CZS pathogenesis. We performed a meta-analysis, gene ontology (GO), and pathway analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during hNPCs infection with ZIKV. We selected three studies (17 samples of infected hPNCs compared to hPNCs uninfected controls) through a systematic search of the Gene Expression Omnibus (GEO) database. The raw reads were trimmed, counted, and normalized. Next, we performed a rank product meta-analysis to detect consistently differentially expressed genes (DEGs) in these independent experiments. We detected 13 statistically significant DEGs. GO ontology and reactome analysis showed an enrichment of interferon, pro-inflammatory, and chemokines signaling and apoptosis pathways in ZIKV-infected cells. Moreover, we detected three possible new candidate genes involved in hNPCs infection: APOL6, XAF1, and TNFRSF1. Our results confirm that interferon (IFN) signaling dominates the ZIKV response, and that a crucial contribution is given by apoptotic pathways, which might elicit the CZS phenotype.

Original languageEnglish
Article number270
JournalMicroorganisms
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Apoptosis
  • Congenital Zika syndrome
  • Gene ontology
  • Genomics
  • Pathway analysis
  • Stem cells
  • Transcriptomics

ASJC Scopus subject areas

  • Microbiology
  • Virology
  • Microbiology (medical)

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