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Nat Commun. 2019 Sep 13;10(1):4155. doi: 10.1038/s41467-019-12063-2.

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

Author information

1
Department of Surgery, Weill Cornell Medical College, 1300 York Ave, New York, NY, 10065, USA.
2
Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Ave, New York, NY, 10065, USA.
3
The SKI Stem Cell Research Facility, The Center for Stem Cell Biology and Developmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY, 10065, USA.
4
Physiology Biophysics and Systems Biology, Weill Cornell Medical College, 1300 York Ave, New York, NY, 10065, USA.
5
Genomics Resources Core Facility, Weill Cornell Medical College, 1300 York Ave, New York, NY, 10065, USA.
6
New York Stem Cell Foundation, 619 W 54th St, New York, NY, 10019, USA.
7
Department of Physiology, Cellular Biology and Immunology, Faculty of Biology, University of Barcelona, Diagonal 643, Barcelona, 08028, Spain.
8
Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Ave, New York, NY, 10065, USA. hes2011@med.cornell.edu.
9
Physiology Biophysics and Systems Biology, Weill Cornell Medical College, 1300 York Ave, New York, NY, 10065, USA. res2025@med.cornell.edu.
10
Department of Surgery, Weill Cornell Medical College, 1300 York Ave, New York, NY, 10065, USA. shc2034@med.cornell.edu.

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.

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