Vertical Transmission of Zika Virus Targeting the Radial Glial Cells Affects Cortex Development of Offspring Mice

Cell Res. 2016 Jun;26(6):645-54. doi: 10.1038/cr.2016.58. Epub 2016 May 13.

Abstract

The recent Zika virus (ZIKV) epidemic in Latin America coincided with a marked increase in microcephaly in newborns. However, the causal link between maternal ZIKV infection and malformation of the fetal brain has not been firmly established. Here we show a vertical transmission of ZIKV in mice and a marked effect on fetal brain development. We found that intraperitoneal (i.p.) injection of a contemporary ZIKV strain in pregnant mice led to the infection of radial glia cells (RGs) of dorsal ventricular zone of the fetuses, the primary neural progenitors responsible for cortex development, and caused a marked reduction of these cortex founder cells in the fetuses. Interestingly, the infected fetal mice exhibited a reduced cavity of lateral ventricles and a discernable decrease in surface areas of the cortex. This study thus supports the conclusion that vertically transmitted ZIKV affects fetal brain development and provides a valuable animal model for the evaluation of potential therapeutic or preventative strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Proliferation
  • Cerebral Cortex / abnormalities
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / pathology
  • Cerebral Cortex / virology*
  • Ependymoglial Cells / pathology*
  • Ependymoglial Cells / virology*
  • Fetus / pathology
  • Fetus / virology
  • Gene Expression Regulation
  • Mice, Inbred C57BL
  • Microcephaly / genetics
  • Microcephaly / pathology
  • Microcephaly / virology
  • Neural Stem Cells / pathology
  • Zika Virus / physiology*
  • Zika Virus Infection / pathology
  • Zika Virus Infection / transmission*
  • Zika Virus Infection / virology