GSE133254
Effect of ZIKV on pre-implantation embryos
To determine the effect of Zika virus infection on pre-implantation embryonic development, we performed single blastocyst RNA-Seq on MOCK and ZIKV infected embryos.   ZIKV infection results in an increased risk of spontaneous abortion and poor intrauterine growth  although the mechanisms underlying fetal loss remain undetermined. Little is known about the  impact of ZIKV infection during the earliest stages of pregnancy, or pre- and peri-implantation,  because most current studies of ZIKV infection in pregnancy models focus on post-implantation  stages. Here, we demonstrate that trophectoderm cells of pre-implantation human and mouse  embryos can be efficiently infected with ZIKV, and that trophectoderm can propagate virus  causing cell death of neural progenitors. These findings were corroborated by our demonstration  that hESC-derived trophectoderm cells are infected by ZIKV in a dose dependent manner. RNAseq of single blastocysts revealed key transcriptional changes in cellular and physiologic functions  upon ZIKV infection, including nervous system development and function, prior to commitment  to the neural cell lineage. Finally, the pregnancy rate of mice infected pre-implantation was > 50%  lower than females infected at E4.5. These results demonstrate that pre-implantation ZIKV  infection of trophectoderm leads to miscarriage or spontaneous abortion. Moreover, pre- and peri-implantation ZIKV infects trophectoderm cells that propagate virus over time causing cell death  in neural progenitors. Cumulatively, these data demonstrate that vertical pre- and peri-implantation  ZIKV infection of trophectoderm impairs fetal development and causes neural progenitor cell  death, elucidating a previously unappreciated association of pre- and peri-implantation ZIKV  infection and microcephaly. Overall design: Single Blastocyst RNASeq of Mock (n=5 samples) and Zika (n=7 samples) infected mouse blastocysts