Zika infection of neural progenitor cells perturbs transcription in neurodevelopmental pathways

PLoS One. 2017 Apr 27;12(4):e0175744. doi: 10.1371/journal.pone.0175744. eCollection 2017.

Abstract

Background: A recent study of the gene expression patterns of Zika virus (ZIKV) infected human neural progenitor cells (hNPCs) revealed transcriptional dysregulation and identified cell cycle-related pathways that are affected by infection. However deeper exploration of the information present in the RNA-Seq data can be used to further elucidate the manner in which Zika infection of hNPCs affects the transcriptome, refining pathway predictions and revealing isoform-specific dynamics.

Methodology/principal findings: We analyzed data published by Tang et al. using state-of-the-art tools for transcriptome analysis. By accounting for the experimental design and estimation of technical and inferential variance we were able to pinpoint Zika infection affected pathways that highlight Zika's neural tropism. The examination of differential genes reveals cases of isoform divergence.

Conclusions: Transcriptome analysis of Zika infected hNPCs has the potential to identify the molecular signatures of Zika infected neural cells. These signatures may be useful for diagnostics and for the resolution of infection pathways that can be used to harvest specific targets for further study.

MeSH terms

  • Down-Regulation
  • Gene Expression Profiling
  • Humans
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / virology
  • Principal Component Analysis
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA / chemistry
  • RNA / isolation & purification
  • RNA / metabolism
  • Sequence Analysis, RNA
  • Signal Transduction
  • Transcriptome*
  • Up-Regulation
  • Zika Virus / pathogenicity*
  • alpha7 Nicotinic Acetylcholine Receptor / genetics
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism

Substances

  • Chrna7 protein, human
  • Protein Isoforms
  • alpha7 Nicotinic Acetylcholine Receptor
  • RNA

Grants and funding

LY was supported by funding from the UCLA/Caltech Medical Scientist Training Program, The Walter and Sylvia Treadway Endowment, and the NIH T32 (NRSA). LP was partially funded by NIH R01 DK094699. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.