Genome-wide CRISPR screen for Zika virus resistance in human neural cells

Proc Natl Acad Sci U S A. 2019 May 7;116(19):9527-9532. doi: 10.1073/pnas.1900867116. Epub 2019 Apr 24.


Zika virus (ZIKV) is a neurotropic and neurovirulent arbovirus that has severe detrimental impact on the developing human fetal brain. To date, little is known about the factors required for ZIKV infection of human neural cells. We identified ZIKV host genes in human pluripotent stem cell (hPSC)-derived neural progenitors (NPs) using a genome-wide CRISPR-Cas9 knockout screen. Mutations of host factors involved in heparan sulfation, endocytosis, endoplasmic reticulum processing, Golgi function, and interferon activity conferred resistance to infection with the Uganda strain of ZIKV and a more recent North American isolate. Host genes essential for ZIKV replication identified in human NPs also provided a low level of protection against ZIKV in isogenic human astrocytes. Our findings provide insights into host-dependent mechanisms for ZIKV infection in the highly vulnerable human NP cells and identify molecular targets for potential therapeutic intervention.

Keywords: CRISPR screen; Zika virus; fetal CNS infection; human pluripotent stem cells; neural progenitors.

Publication types

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

MeSH terms

  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Astrocytes / virology
  • CRISPR-Cas Systems*
  • Cell Line
  • Disease Resistance / genetics*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology
  • Neural Stem Cells / virology*
  • Virus Replication / genetics*
  • Zika Virus / physiology*
  • Zika Virus Infection / genetics*
  • Zika Virus Infection / metabolism
  • Zika Virus Infection / pathology