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


Authors: Tan, L.; Lacko, L. A.; Zhou, T.; Tomoiaga, D.; Hurtado, R.; Zhang, T.; Sevilla, A.; Zhong, A.; Mason, C. E.; Noggle, S.; Evans, T.; Stuhlmann, H.; Schwartz, R. E.; Chen, S.
Article Title: Pre- and peri-implantation Zika virus infection impairs fetal development by targeting trophectoderm cells
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.
Journal Title: Nature Communications
Volume: 10
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2019-09-13
Start Page: 4155
Language: English
DOI: 10.1038/s41467-019-12063-2
PUBMED: 31519912
PROVIDER: scopus
PMCID: PMC6744420
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Ting Zhou
    2 Zhou
  2. Aaron Zhong
    1 Zhong