# Innate Immune Regulation of Zika Virus Infection

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $813,373

## Abstract

PROJECT SUMMARY/ABSTRACT
Zika virus (ZIKV) is a flavivirus that has recently emerged from Uganda, into Asia, across the Pacific and now
into the Americas. ZIKV infection is transmitted to humans by the bite of an infected mosquito. Person to person
sexual transmission of ZIKV has also been documented. ZIKV infection poses a major threat to unborn children
because it efficiently crosses the placental barrier to mediate maternal to fetal transmission in utero. Fetal
infection can lead to varied pathologies including microcephaly and fetal death. Little is known of how placental
cells respond to infection to control ZIKV tropism and to mount innate immune defenses to protect against ZIKV
spread and fetal infection. Our preliminary studies show that ZIKV triggers placental innate immune activation
through RIG-I sensing of viral pathogen associated molecular patterns (PAMPS) but that it directs a broad
blockade to cytokine signaling through signal transducer and activator of transcription (STAT) proteins in the
infected cell. This broad STAT suppression attenuates interferon (IFN) innate immune defenses to support virus
replication and spread to the fetus. This proposal will investigate the central hypotheses that the outcome of
ZIKV infection and disease is linked with regulation of innate immune defenses and control of JAK-STAT
signaling, and that viral evasion of host defenses enables maternal-fetal ZIKV transmission and fetal disease.
We will conduct three Aims: 1) Determine the molecular mechanisms by which ZIKV induces innate immune
responses in key cell types of the maternal-fetal interface throughout human pregnancy; 2) Determine the
molecular mechanisms of broad JAK-STAT regulation by ZIKV, and 3) Define the role of innate immune
activation and STAT regulation of antiviral defenses to control ZIKV infection of human placental cells ex vivo,
and determine how viral innate immune evasion impacts fetal disease in the STAT2-KI model of maternal/fetal
transmission.

## Key facts

- **NIH application ID:** 9881246
- **Project number:** 5R01AI145296-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Carolyn B Coyne
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $813,373
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881246

## Citation

> US National Institutes of Health, RePORTER application 9881246, Innate Immune Regulation of Zika Virus Infection (5R01AI145296-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9881246. Licensed CC0.

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