# Project 1:  Impact of sustained ZIKV viremia in pregnancy

> **NIH NIH P01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $416,737

## Abstract

Project 1 - Project Summary/Abstract
Infection with Zika virus (ZIKV) has been associated with an increased incidence of a spectrum of birth
defects in Brazil. Natural infection in pregnant women, and experimental infection in rhesus macaques
has demonstrated that pregnancy is associated with prolonged viremia, in comparison with infection of
nonpregnant individuals. In our published and unpublished studies, we have found that maternal infec-
tion with ZIKV in the first but not the third trimester results in inflammation tissue damage in the visual
system (choroid, retina, optic nerve), and in one case, severe developmental malformations of the fetal
eye. In addition, regardless of the gestational stage of infection, there vertical transmission to the fetus
was common. Thus, there may be a more significant risk to the fetus in areas where ZIKV and the mos-
quito vector is endemic than is currently appreciated.
Rigorous examination of maternal viremia and fetal growth and development, and comprehensive eval-
uation of neonatal sensorineural characteristics and viral burden will not be possible in human clinical
settings. The nonhuman primate offers an outstanding opportunity to gain insight into pathophysiologi-
cal processes in fetal infection with ZIKV. Our overall hypothesis is that duration of maternal viremia >28
provides unequivocal evidence of vertical transmission is associated with elevated fetal risk for infection
and thus, fetal neurodevelopmental impact. To link maternal viremia and fetal ZIKV infection, we pro-
pose two Specific Aims.
 Specific Aim 1. To determine the impact of maternal ZIKV viremia on fetal development in utero, as
 assessed by fetal growth, vertical transmission, and tissue damage.
 Specific Aim 2. To define the impact of in utero ZIKV transmission on the incidence of birth defects.
We will assess maternal viremia and fetal growth, and associate maternal viremia and the maternal
immune response with the impact on the fetus, using ultrasound to monitor fetal development. We will
evaluate neonates for malformations of, and assess functional deficits in visual, auditory, and behavioral
capacity. Viral distribution and tissue histopathology will be determined at necropsy. The development
of this model to study impact of maternal infection on neonatal sensorineural injury will be a valuable
step forward in building the nonhuman primate platform for studying interactions with DENV in Project
2, and testing therapeutic interruption of these fetal effects with antibody treatments in Project 3.

## Key facts

- **NIH application ID:** 10220702
- **Project number:** 5P01AI132132-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** THADDEUS G GOLOS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $416,737
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220702

## Citation

> US National Institutes of Health, RePORTER application 10220702, Project 1:  Impact of sustained ZIKV viremia in pregnancy (5P01AI132132-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10220702. Licensed CC0.

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