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

TitlePre- and peri-implantation Zika virus infection impairs fetal development by targeting trophectoderm cells.
Publication TypeJournal Article
Year of Publication2019
AuthorsTan, L, Lacko, LA, Zhou, T, Tomoiaga, D, Hurtado, R, Zhang, T, Sevilla, A, Zhong, A, Mason, CE, Noggle, S, Evans, T, Stuhlmann, H, Schwartz, RE, Chen, S
JournalNat Commun
Volume10
Issue1
Pagination4155
Date Published2019 09 13
ISSN2041-1723
KeywordsAbortion, Spontaneous, Animals, Blastocyst, Embryo Implantation, Female, Fetal Development, Humans, Mice, Mice, Inbred C57BL, Pregnancy, Pregnancy Complications, Infectious, RNA, Viral, Translational Medical Research, Trophoblasts, Zika Virus, Zika Virus Infection
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.

DOI10.1038/s41467-019-12063-2
Alternate JournalNat Commun
PubMed ID31519912
PubMed Central IDPMC6744420
Grant ListDP3 DK111907 / DK / NIDDK NIH HHS / United States
R03 DK117252 / DK / NIDDK NIH HHS / United States
P01 HD067244 / HD / NICHD NIH HHS / United States
F32 HD096810 / HD / NICHD NIH HHS / United States
R01 DK116075 / DK / NIDDK NIH HHS / United States
R01 MH117406 / MH / NIMH NIH HHS / United States
R21 DK116171 / DK / NIDDK NIH HHS / United States
K08 DK101754 / DK / NIDDK NIH HHS / United States
R01 DK119667 / DK / NIDDK NIH HHS / United States