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Pre- and peri-implantation Zika virus infection impairs fetal development by targeting trophectoderm cells.
- Source :
-
Nature communications [Nat Commun] 2019 Sep 13; Vol. 10 (1), pp. 4155. Date of Electronic Publication: 2019 Sep 13. - Publication Year :
- 2019
-
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.
- Subjects :
- Abortion, Spontaneous metabolism
Abortion, Spontaneous physiopathology
Animals
Blastocyst cytology
Blastocyst metabolism
Embryo Implantation physiology
Female
Fetal Development genetics
Fetal Development physiology
Humans
Mice
Mice, Inbred C57BL
Pregnancy
RNA, Viral genetics
Translational Research, Biomedical methods
Trophoblasts cytology
Trophoblasts metabolism
Pregnancy Complications, Infectious metabolism
Zika Virus pathogenicity
Zika Virus Infection complications
Zika Virus Infection metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31519912
- Full Text :
- https://doi.org/10.1038/s41467-019-12063-2