# Dynamics and immune control of norovirus infection in neonatal mice

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2022 · $32,686

## Abstract

Project Summary/Abstract
Norovirus (NoV) is the leading global cause of acute gastroenteritis, associated with an estimated 685 million
cases annually. NoV infects individuals of all ages but infection is most severe in children under the age of 5,
causing approximately 50,000 deaths in this population each year. Young children also experience prolonged
fecal shedding with high viral loads, playing a key role in transmission throughout the entire population. However,
the host factors which contribute to variability in NoV severity and shedding by age are not well-defined.
Murine NoV (MNoV) is used as a model to study viral pathogenesis in vivo, but almost all studies have been
conducted in adult mice. The overarching objective of this work is to use neonatal mice as a model to understand
the dynamics and immune control of NoV in young animals. Preliminary studies suggest that the cellular and
tissue tropism of persistent MNoV infection is altered in neonatal mice compared to adult mice. Further, innate
immune responses are central to controlling viral infection in neonates. Neonatal Stat1-/- mice, which lack a
transcription factor necessary for interferon signaling, shed higher levels of MNoV and succumb to infection. This
lethality is unique to young animals, as adult Stat-/- mice typically survive infection with persistent strains of MNoV.
The overall hypothesis of this proposal is that IFN responses limit MNoV replication and tropism in neonates,
thereby controlling fecal shedding and lethality. We will test this hypothesis using our neonatal model of MNoV
infection. In Aim 1, we will define the kinetics of viral replication and shedding of infectious virions and define the
cellular tropism of MNoV in wild-type and Stat1-/- neonates. In Aim 2, we will characterize the timing, localization,
and function of individual IFN responses and whether IFN responses control viral mutation and/or extraintestinal
dissemination. These studies will help explain host factors which contribute to variation in viral pathogenesis and
persistent shedding by age and will represent a significant advancement into understanding the differences in
enteric virus dynamics between adults and children.
This work will take place at Washington University in St. Louis, which provides exceptional access to the
resources and training necessary to complete these studies. Access to cutting-edge facilities such as the Center
for Cellular Imaging and DNA Sequencing Innovation lab, as well as ample training opportunities available from
on-campus core facilities, make these experiments technically possible. Support from the Molecular Microbiology
and Microbial Pathogenesis program and mentorship from sponsors and other faculty on campus will ensure the
successful completion of the proposed research.

## Key facts

- **NIH application ID:** 10386562
- **Project number:** 1F31AI167499-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Elizabeth Alexandra Kennedy
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $32,686
- **Award type:** 1
- **Project period:** 2021-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386562

## Citation

> US National Institutes of Health, RePORTER application 10386562, Dynamics and immune control of norovirus infection in neonatal mice (1F31AI167499-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10386562. Licensed CC0.

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