# Defining the Role of the Neonatal Fc Receptor in a Novel Model of Echovirus II Infection

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $33,220

## Abstract

PROJECT SUMMARY
Enteroviruses are a significant growing public health concern. Enteroviruses, such as poliovirus, coxsackievirus
B (CVB), echoviruses and enterovirus 71 (EV71), typically cause minor symptoms. However, neonates and
children are particularly susceptible to severe enterovirus infections, which are characterized by neurological
complications such as encephalitis, meningitis, and paralysis. In addition, neonatal infections of echovirus 11
(E11) result in liver failure, which lead to death of the neonate. These single-stranded RNA viruses are primarily
transmitted through the fecal-oral route, targeting the gastrointestinal (GI) tract. After replication in the GI
epithelium, these viruses disseminate into secondary target tissues such as the brain, pancreas, and liver. Many
enteroviruses lack comprehensive mouse models that would allow a better understanding of pathogenesis in
animals. Therefore, it is necessary to develop additional mouse models that accurately mimic the complexity of
interactions in the GI epithelium as well as establishing more complete mouse models for certain enteroviruses
to study pathogenesis at secondary sites of infection. Currently, only a few mouse models of E11 infection exist
but they do not model infection at secondary sites such as the liver. In previous studies, we have identified a
pan-echovirus receptor, the neonatal Fc receptor (FcRn). We showed that human transgenic neonatal mice
expressing FcRn (hFcRnTg) were more susceptible to oral echovirus 11 (E11) infection. I have established an
adult mouse model of disease where E11 infects the liver, a key site in human infection. I hypothesize that after
dissemination from the GI tract, E11 infects Kupffer Cells (KCs) in the liver in an FcRn-dependent manner,
resulting in tissue damage to the liver. Here, I seek to determine the cell tropism of E11 in the liver. I will use in
vitro and in vivo models to elucidate these tropisms in the liver. Mouse models using hFcRnTg, mFcRn (WT), and
FcRn-/- animals will be used to understand the cellular tropism and the role of FcRn in infection. Additionally, I
want to understand how this cellular tropism influences functionality of the liver. In this aim, I will assess whether
infection can mediate cell death in the liver and whether liver enzymes are elevated during infection, suggesting
liver dysfunction. In addition, I seek to appreciate the innate immune response to E11 in the liver. I will use mouse
models that are deficient in type I or III interferon signaling to assess the role of IFNs in E11 infection of the liver.
These proposed studies will be one of the first to define the cellular tropism and the antiviral response to E11
infection in a secondary site of infection such as the liver.

## Key facts

- **NIH application ID:** 10375352
- **Project number:** 5F31AI149866-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Alexandra Wells
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,220
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-04-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375352

## Citation

> US National Institutes of Health, RePORTER application 10375352, Defining the Role of the Neonatal Fc Receptor in a Novel Model of Echovirus II Infection (5F31AI149866-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10375352. Licensed CC0.

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