# Mechanistic Analysis of Zika Virus Induced Placental Damage During Pregnancy

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $670,716

## Abstract

PROJECT SUMMARY
 The recent outbreak of Zika virus (ZIKV), a mosquito-borne flavivirus, in the western hemisphere resulted
in a serious public health threat, in particular for pregnant women due to the subsequent Congenital Zika
Syndrome which can manifest in infected fetuses. The placenta plays a central role in fetal susceptibility to
maternal viral infections yet the timing of, and the mechanisms contributing to, placental injury following ZIKV
infection are unknown. We have utilized a nonhuman primate (NHP) model of ZIKV infection during pregnancy
to demonstrate functional abnormalities in placental oxygen transport, which likely constrain normal fetal organ
development and predispose to growth abnormalities. Decreased oxygen permeability of the placental villi
appears to be a consequence of uterine vasculitis, stromal cell death and placental villous damage. Despite a
robust inflammatory response following ZIKV infection in both early and late gestation, we have shown that ZIKV
persists for weeks to months in maternal-placental-fetal tissues, which highlights the need to investigate
preventative strategies that can be employed during pregnancy. Vaccination is an efficient and tractable strategy
for combating viral pathogens. The clinical restrictions imposed during pregnancy make the safest vaccine
platforms utilizing antigens, which include virus-like particles (VLP), a high value target for development. We
have recently generated a VLP-based vaccine against ZIKV by purifying VLP secreted by cells expressing the
ZIKV prM-E polyprotein.
 Uterine and placental macrophages play a key role in maintaining normal pregnancy and have been
shown to be susceptible to productive infection by ZIKV in cell culture systems. Moreover, in our NHP model we
demonstrated changes in placental macrophage phenotype following ZIKV infection. We hypothesize that ZIKV
targets placental macrophages, causes acute direct (viral) and indirect (immunopathological) damage to the
placenta during development, which activates cellular components responsible for wound healing and may cause
oxidative damage within the placental villous. These induced changes result in placental vascular adaptations,
and tissue injury which impairs transport and detrimentally impacts fetal growth and development. The objective
of this proposal is to temporally characterize the progression of ZIKV-mediated changes in placental function
and tissue damage. Our longitudinal approach will facilitate characterization of disease pathogenesis in both the
placenta and fetus by combining advanced functional imaging with temporal profiling of the fetal immune
response, tissue transcriptomics following infection, and implementation of a novel vaccine to determine whether
vaccination can mitigate placental and fetal injury.

## Key facts

- **NIH application ID:** 9934261
- **Project number:** 5R01HD096741-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Antonio E Frias
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $670,716
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934261

## Citation

> US National Institutes of Health, RePORTER application 9934261, Mechanistic Analysis of Zika Virus Induced Placental Damage During Pregnancy (5R01HD096741-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934261. Licensed CC0.

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