# Transgenic mouse core

> **NIH NIH U19** · ROCKEFELLER UNIVERSITY · 2021 · $235,347

## Abstract

ABSTRACT – Core A, Bournazos
The ability of an IgG antibody to mediate biological effects in vivo, such as protection from viral infection, results
from its bispecific nature. The Fab region of an antibody recognizes epitopes on the viral spike and may interfere
with virus binding to target cells, while the Fc domain mediates diverse immunomodulatory activities through
specific interactions with Fcγ receptors (FcγRs) expressed by effector leukocytes. Studies on several infectious
pathogens have shown that Fc-FcγR interactions have the capacity to mediate a wide spectrum of opposing
functions – from viral opsonization and clearance of infected cells (protective) to enhanced viral infection and
disease severity (pathogenic). Understanding the precise mechanisms by which IgG antibodies mediate
protective or pathogenic functions necessitates the use of well-defined in vivo experimental systems that reflect
the unique complexity of effector leukocytes that participate in an immune response. Indeed, although in vitro
assays using cell lines or primary effector cells represent well-established approaches for characterizing the
function of IgG antibodies, such assays provide limited information on the precise molecular mechanisms that
drive human immunity during infection or upon vaccination. We will provide a Core that will maintain,
characterize, and distribute a series of genetically-engineered humanized mouse strains to the Center
investigators in support of the proposed studies on the characterization of the pathogenic activity of anti-flavivirus
antibodies that confer susceptibility to dengue disease, as well as on the evaluation of the protective antiviral
function of neutralizing antibodies against hepatitis B viruses. Through specific deletions of key immune signaling
pathways or reconstitution with human primary cells that represent the natural viral host cell type, these
engineered mouse strains support the infection and replication of flaviviruses and hepatitis viruses in vivo,
thereby facilitating the study of viral disease pathogenesis, as well as the characterization of the molecular
mechanisms that contribute to the IgG antibody activity during viral infection.

## Key facts

- **NIH application ID:** 10134212
- **Project number:** 5U19AI111825-08
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Stylianos Bournazos
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $235,347
- **Award type:** 5
- **Project period:** 2014-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134212

## Citation

> US National Institutes of Health, RePORTER application 10134212, Transgenic mouse core (5U19AI111825-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10134212. Licensed CC0.

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