In utero infection of Zika virus leads to abnormal central nervous system development in mice

Sci Rep. 2019 May 13;9(1):7298. doi: 10.1038/s41598-019-43303-6.

Abstract

The World Health Organization has declared ZIKA virus (ZIKV) a global public health emergency, prompted by the association of ZIKV infections with severe brain abnormalities in the human fetus. ZIKV preferentially targets human neuronal precursor cells (NPCs) in both monolayer and cortical brain organoid culture systems and stunts their growth. Although ZIKV is well recognized to cause microcephaly, there is no systematic analysis to demonstrate the effect of ZIKV on central nervous system (CNS) development, including brain malformations and spinal cord dysfunction. Here, we conducted a longitudinal analysis to show that a novel mouse model (infected in utero and monitored after birth until adulthood) recapitulates the effects of ZIKV infection affecting neural stem cells fate and leads to a thinner cortex and a smaller brain. Furthermore, we demonstrate the effect of ZIKV on spinal cord function. Specifically, we found significant reductions in neuron numbers in the anterior horn of grey matter of the spinal cord and muscle dystrophy with a significant decrease in forepaw grip strength in the ZIKV group. Thus, the established mouse model of ZIKV infection leading to abnormal CNS development will help to further advance our understanding of the disease pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / embryology
  • Brain / virology
  • Cell Count
  • Disease Models, Animal
  • Extremities / physiopathology
  • Female
  • Humans
  • Mice
  • Microcephaly / pathology
  • Microcephaly / virology*
  • Muscle Strength / physiology
  • Muscular Dystrophy, Animal / pathology
  • Muscular Dystrophy, Animal / physiopathology
  • Muscular Dystrophy, Animal / virology*
  • Neural Stem Cells / pathology
  • Neural Stem Cells / virology
  • Neurons / pathology
  • Neurons / virology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / pathology
  • Prenatal Exposure Delayed Effects / virology*
  • Spinal Cord Ventral Horn / cytology
  • Spinal Cord Ventral Horn / embryology
  • Spinal Cord Ventral Horn / virology
  • Zika Virus / isolation & purification
  • Zika Virus / pathogenicity*
  • Zika Virus Infection / complications*
  • Zika Virus Infection / virology