# Effect of Pre- and Peri-Implantation Zika Virus Infection on Fetal Development

> **NIH NIH F32** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $69,306

## Abstract

PROJECT SUMMARY Lauretta A. Lacko, F32 Resubmission, 8/8/2018
Perinatal infections are a major cause of maternal and fetal illness, accounting for 2-3% of all congenital
abnormalities. Zika virus (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 pre- and peri-implantation because most current studies in pregnancy
models focus on post-implantation stages. The recent ZIKV epidemic is a growing public health concern as
infection in pregnant woman not only causes abortion and poor growth, but also severe neurological
consequences such as microcephaly. Notably, the most severe fetal abnormalities have been associated with
infection during the first and second trimester of pregnancy. Given the rapid emergence of this devastating
infectious disease, there is an urgent need to determine the in utero pathogenesis of ZIKV during early
gestation. The overall objective of this study is to determine the effect of ZIKV infection at the earliest stages of
pregnancy, or pre- and peri-implantation, on fetal and placental development, and to shed insight into possible
mechanisms by which early infection increases risk of the disease. Recent studies have demonstrated ZIKV
can infect first trimester immortalized trophoblast cell line and placental explants, but not mature human
trophoblasts or explants isolated from late stage pregnancies. We hypothesize that trophectoderm cells (TECs)
are a route for efficient mother to fetus viral transmission during early pregnancy, and can propagate the virus
to further infect developing neural progenitor cells over time. Indeed, our preliminary studies (manuscript under
peer review) demonstrate that ex vivo infection of murine blastocysts and human pre-implantation embryos
results in efficient infection of TECs. Further, pre- and peri-implantation ZIKV infection can induce neural
progenitor cell death at mid-gestation. In this proposal, we will define the cellular response of TECs to ZIKV
infection in vivo (Aim 1) and dissect the molecular mechanism controlling ZIKV infection by studying the
candidate genes identified from a CRISPR-based whole genome wide gene knockout screen (Aim 2). We will
combine immunostaining, gene expression, and gene editing technologies to address these questions. These
studies will provide fundamental insight into vertical transmission of ZIKV during the earliest stages of
gestation. More importantly, it will shed a light into the mechanism regulating flavivirus and/or other viral
infections during pregnancy.

## Key facts

- **NIH application ID:** 10001331
- **Project number:** 5F32HD096810-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Lauretta A. Lacko
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,306
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001331

## Citation

> US National Institutes of Health, RePORTER application 10001331, Effect of Pre- and Peri-Implantation Zika Virus Infection on Fetal Development (5F32HD096810-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001331. Licensed CC0.

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