Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells

PLoS Negl Trop Dis. 2021 Mar 3;15(3):e0009183. doi: 10.1371/journal.pntd.0009183. eCollection 2021 Mar.

Abstract

Global Zika virus (ZIKV) outbreaks and their strong link to microcephaly have raised major public health concerns. ZIKV has been reported to affect the innate immune responses in neural stem/progenitor cells (NS/PCs). However, it is unclear how these immune factors affect neurogenesis. In this study, we used Asian-American lineage ZIKV strain PRVABC59 to infect primary human NS/PCs originally derived from fetal brains. We found that ZIKV overactivated key molecules in the innate immune pathways to impair neurogenesis in a cell stage-dependent manner. Inhibiting the overactivated innate immune responses ameliorated ZIKV-induced neurogenesis reduction. This study thus suggests that orchestrating the host innate immune responses in NS/PCs after ZIKV infection could be promising therapeutic approach to attenuate ZIKV-associated neuropathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / immunology
  • Brain / virology
  • Cell Differentiation
  • Cell Proliferation
  • Humans
  • Immunity, Innate*
  • Neural Stem Cells / immunology
  • Neural Stem Cells / virology*
  • Neurogenesis / immunology
  • Virus Replication
  • Zika Virus / physiology*
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / virology