# Pathways of vertical Zika virus transmission in nonhuman primate pregnancy

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $739,250

## Abstract

Infection with Zika virus (ZIKV) in pregnancy has been associated with an increased incidence of a spectrum of
birth defects collectively referred to as Congenital Zika Syndrome (CZS). We have demonstrated that the
rhesus macaque is susceptible to ZIKV strains of French Polynesian, African, and American (Puerto Rican)
origin, and our published and unpublished work has shown that vertical transmission in rhesus macaques is
highly efficient: 5 of 5 fetuses, whether maternal infection was administered in the first or the third trimester,
resulted in detectable vRNA in fetal tissues, and histopathology (chiefly inflammation) in fetal organs.
Nonetheless, there is minimal understanding of the pathway by which ZIKV traverses the maternal-fetal barrier
in vivo. Understanding how virus is afforded access to the fetal compartment will allow consideration of
possible interventions. We have revised this proposal to study vertical transmission in the rhesus monkey
during the first month after maternal infection to directly address this need, with the following Specific Aims.
Specific Aim 1. To determine the pathway by which ZIKV transits the maternal-fetal interface in vertical
transmission in vivo by assessing viral RNA burden in maternal, placental and fetal tissues.
Specific Aim 2. To define the cellular impact of ZIKV infection by assessing tissue histopathology in parallel
with virus localization at the maternal-fetal interface and in fetal tissues.
Specific Aim 3. To define decidual leukocyte and placental Hofbauer cell populations with high-dimensional
flow cytometry, and directly assess ZIKV infection with intracellular ZIKV antigen staining.
With these Aims we will use the NHP model to comprehensively advance our understanding of the pathway
and trajectory of vertical transmission of ZIKV. We will define the viral burden at the maternal-fetal interface
during the processes leading to fetal infection. We will identify the cellular compartments which contain ZIKV
protein and replicating virus. Finally, we will define the immunological responses in the maternal decidua and
the fetal placenta during vertical transmission. To accomplish these goals, we will work with a team of expert
NHP virologists who have established the macaque model of ZIKV infection, and pathologists and reproductive
immunologists who can provide expert and comprehensive assessment of both maternal and fetal outcomes of
ZIKV infection. The development of therapies requires insight into pathogenesis. By defining the pathway(s) of
vertical transmission, we will have established a relevant NHP experimental platform for testing
approaches to interrupt vertical transmission and the development of CZS in human infants.

## Key facts

- **NIH application ID:** 10369653
- **Project number:** 5R01AI132519-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Emma L Mohr
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $739,250
- **Award type:** 5
- **Project period:** 2018-04-25 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369653

## Citation

> US National Institutes of Health, RePORTER application 10369653, Pathways of vertical Zika virus transmission in nonhuman primate pregnancy (5R01AI132519-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10369653. Licensed CC0.

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