Zika virus alters DNA methylation status of genes involved in Hippo signaling pathway in human neural progenitor cells

Epigenomics. 2019 Aug;11(10):1143-1161. doi: 10.2217/epi-2018-0180. Epub 2019 Jun 25.

Abstract

Aim: This study was aimed to understand if Zika virus (ZIKV) alters the DNA methylome of human neural progenitor cells (hNPCs). Materials & methods: Whole genome DNA methylation profiling was performed using human methylationEPIC array in control and ZIKV infected hNPCs. Results & conclusion: ZIKV infection altered the DNA methylation of several genes such as WWTR1 (TAZ) and RASSF1 of Hippo signaling pathway which regulates organ size during brain development, and decreased the expression of several centrosomal-related microcephaly genes, and genes involved in stemness and differentiation in human neural progenitor cells. Overall, ZIKV downregulated the Hippo signaling pathway genes which perturb the stemness and differentiation process in hNPCs, which could form the basis for ZIKV-induced microcephaly.

Keywords: DNA methylation; Hippo signaling; RASSF1; YAP/TAZ; Zika virus; human neural progenitor cells; microcephaly; stemness and differentiation.

MeSH terms

  • Biomarkers / analysis*
  • Cell Differentiation*
  • Cells, Cultured
  • DNA Methylation*
  • Gene Expression Regulation*
  • Hippo Signaling Pathway
  • Humans
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / virology
  • Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Zika Virus / physiology
  • Zika Virus Infection / genetics
  • Zika Virus Infection / metabolism
  • Zika Virus Infection / virology*

Substances

  • Biomarkers
  • RASSF1 protein, human
  • Trans-Activators
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Tumor Suppressor Proteins
  • WWTR1 protein, human
  • Protein Serine-Threonine Kinases