# IL-1β regulation of Zika-mediated adverse perinatal outcomes

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $597,355

## Abstract

SUMMARY
Zika virus (ZIKV) infection of pregnant females results in congenital infection of offspring and long-term
developmental birth defects. Using an immunocompetent mouse model that we developed (published in
Nature Communications), we have shown that intrauterine infection with either African, American, or Asian
strains of ZIKV during early, but not late, pregnancy causes infection of the placenta and fetuses, placental
inflammation, neonatal cortical thinning, and short-term neurologic deficits in offspring. More recently, we have
demonstrated that placental IL-1β concentrations are elevated in ZIKV-infected dams, and we can reverse the
ZIKV-associated short-term neurobehavioral sequelae in offspring by blocking IL-1 receptor signaling during
the infection. We hypothesize that placental inflammation following intrauterine ZIKV infection causes perinatal
neurological injury, which can then be reversed by targeting maternal IL-1β signaling. While most ZIKV
interventions focus on antivirals and vaccines to limit perinatal ZIKV infection, to date no studies have
considered the role of maternal and placental inflammation as a mechanism mediating long-term adverse
perinatal outcomes following ZIKV infection. Specific Aim 1 will assess the mechanisms mediating elevated IL-
1β signaling in the placenta at different gestational ages following ZIKV infection, the long-term downstream
effects of the placental immunopathology and placental IL-1β signaling, and whether these effects are sex-
specific. In particular, Aim 1 will determine how placental inflammasome activation, IL-1β release, or
engagement of the IL-1 receptor lead to adverse perinatal outcomes. Specific Aim 2 will examine the
importance of maternal as opposed to fetal IL-1β signaling in the pathogenesis of perinatal brain injury
following ZIKV infection. Using embryo transfer of IL-1β signaling deficient and wild type mouse strains, Aim 2
will assess whether IL-1β activity of maternal origin is critical for sex-specific fetal brain injury. Our novel
translational research proposal, utilizing a ZIKV model that we developed, will have a significant impact on
perinatal medicine as it will lead to a better understanding of the role of placental inflammation in the
pathogenesis of fetal congenital diseases caused by infection or other inflammatory states during pregnancy.

## Key facts

- **NIH application ID:** 10189676
- **Project number:** 5R01HD097608-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** IRINA BURD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $597,355
- **Award type:** 5
- **Project period:** 2018-09-21 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189676

## Citation

> US National Institutes of Health, RePORTER application 10189676, IL-1β regulation of Zika-mediated adverse perinatal outcomes (5R01HD097608-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10189676. Licensed CC0.

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