# Determining how macrophages regulate immunity to Zika virus infection at the maternal-fetal interface

> **NIH NIH U01** · EMORY UNIVERSITY · 2021 · $439,360

## Abstract

ABSTRACT
The placenta is characterized by intimate contact between the maternal blood and fetal chorionic villi. This
organ is a target for rubella, cytomegalovirus, herpes simplex, HIV-1, hepatitis B and C viruses and parvovirus
B19 infection, by either direct or contiguous infection of placental cell layers, virion passage through a breach
or by cell-associated transport. Most recently, Zika virus (ZIKV), a mosquito-borne flavivirus of significant public
health concern in the Americas, was found to transmit from an infected mother
to the developing fetus in utero
,
resulting in adverse pregnancy outcomes characterized by fetal brain abnormalities and microcephaly. The
greatest risk of serious fetal sequelae is associated with ZIKV infection early in pregnancy, suggesting
enhanced tropism for placental cells during the first- and second-trimester. However the mechanism by which
ZIKV establishes placental and fetal infection is poorly understood. We seek to fill this gap in knowledge and
develop a deeper mechanistic understanding for how macrophages in the maternal-fetal compartment maintain
immune homeostasis and restrict ZIKV transmission to the developing fetus. ZIKV antigen has been detected
in chronic villi, specifically within placental macrophages or Hofbauer cells (HCs) and histiocytes from women
who gave birth to infants with microcephaly or had active ZIKV infection during pregnancy. ZIKV RNA has also
been isolated from placental tissue in humans and from pregnant mice infected with ZIKV. Several studies,
including one recently published by our group, identified HCs as target cells of viral infection in vivo and in
vitro. We showed that primary human HCs isolated from full-term placentae are permissive to productive
infection by a contemporary strain of ZIKV, PRVABC59 (PR 2015). Upon ZIKV infection, HCs produced IFN-α
and pro-inflammatory cytokines, however, we observed little to no cell death. Our findings were the first to
identify a permissive cell type for ZIKV infection in the placenta, however, it is still unclear what role decidual or
fetal monocyte-derived macrophages play during ZIKV infection and whether these placental cells dynamically
change during pregnancy to program more potent antiviral responses to virus infection later in pregnancy.
Based on our preliminary studies, our proposal will address the central hypothesis that macrophages in the
maternal-fetal compartment (decidual, placental and fetal) in early gestation are more permissive for ZIKV
infection and replication as compared to late-gestation macrophages, directly corresponding to reduced
potency of cell autonomous antiviral immune signaling. Our proposal is divided into two specific aims that seek:
1) To define the dynamics of innate immune signaling in macrophages at the maternal-fetal interface during
pregnancy; and 2) To determine how macrophages in the maternal-fetal compartment control ZIKV infection
during pregnancy. These studies will provide new insights...

## Key facts

- **NIH application ID:** 10107728
- **Project number:** 5U01AI131566-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rana Chakraborty
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $439,360
- **Award type:** 5
- **Project period:** 2017-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107728

## Citation

> US National Institutes of Health, RePORTER application 10107728, Determining how macrophages regulate immunity to Zika virus infection at the maternal-fetal interface (5U01AI131566-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10107728. Licensed CC0.

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