Pre- and peri-implantation Zika virus infection impairs fetal development by targeting trophectoderm cells. Academic Article uri icon

Overview

abstract

  • Zika virus (ZIKV) infection results in an increased risk of spontaneous abortion and poor intrauterine growth although the underlying mechanisms remain undetermined. Little is known about the impact of ZIKV infection during the earliest stages of pregnancy, at pre- and peri-implantation, because most current ZIKV pregnancy studies have focused on post-implantation stages. Here, we demonstrate that trophectoderm cells of pre-implantation human and mouse embryos can be infected with ZIKV, and propagate virus causing neural progenitor cell death. These findings are corroborated by the dose-dependent nature of ZIKV susceptibility of hESC-derived trophectoderm cells. Single blastocyst RNA-seq reveals key transcriptional changes upon ZIKV infection, including nervous system development, prior to commitment to the neural lineage. The pregnancy rate of mice is >50% lower in pre-implantation infection than infection at E4.5, demonstrating that pre-implantation ZIKV infection leads to miscarriage. Cumulatively, these data elucidate a previously unappreciated association of pre- and peri-implantation ZIKV infection and microcephaly.

publication date

  • September 13, 2019

Research

keywords

  • Pregnancy Complications, Infectious
  • Zika Virus
  • Zika Virus Infection

Identity

PubMed Central ID

  • PMC6744420

Scopus Document Identifier

  • 85072165464

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-12063-2

PubMed ID

  • 31519912

Additional Document Info

volume

  • 10

issue

  • 1