# A Rabbit Model of Epstein-Barr Virus Infection

> **NIH NIH R21** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2022 · $242,118

## Abstract

PROJECT SUMMARY
 Epstein-Barr virus (EBV) is a herpesvirus that persists as a notable human pathogen with significant
oncogenic potential that is related to its ability to establish lifelong latent infection within an immunocompetent
host. Unlike for the vast majority of viruses, EBV-associated diseases are almost exclusively a consequence of
latent infection instead of damage caused by virus replication. Latency poses significant problems, for example,
in the development of effective anti-EBV therapeutics, since the majority of such compounds are designed to
target viral polymerases and other proteins active only during virus replication; novel approaches are therefore
needed to target latent EBV infection. Moreover, the ubiquitous nature of EBV (~95% infected by adulthood) and
the highly evolved equilibrium that it has established within the human immune system, make development of
an effective vaccine challenging. Both of these challenges could be greatly aided by a biologically accurate and
tractable animal model of EBV infection, which currently does not exist. Surprisingly, several reports over the
last decade have provided support for the laboratory rabbit as a model of EBV infection. In preliminary work, we
have confirmed the most salient observations from these earlier studies, confirming that rabbits are indeed
infectable, as indicated by persistence of the viral genome and expression of EBV genes associated with both
the latent and productive stages of the virus lifecycle. However, several critical demonstrations are required to
support authenticity of this model, and thus the extent to which it could be applied experimentally. In this
application, we propose three specific aims to fill these gaps through complementary efforts by two senior
investigators in the EBV field, and a third who has considerable expertise in the use of the rabbit as a model for
virus infection and immune-related studies. Under Aim 1, Dr. Clare Sample will assess EBV infection in the
epithelial cell component of the lifecycle, including the use of organotypic (raft) cultures of primary epithelium, a
model she has developed and used to define EBV infection in human epithelium. Under Aim 2, Dr. Jeffery
Sample will employ his expertise in the field of EBV latency to direct studies to elucidate whether establishment
of a persistent infection in rabbit B cells is mechanistically comparable to the process that occurs in the human
B-cell compartment. Finally, Dr. Neil Christensen, employing his expertise with the rabbit model will support work
under Aims 1 and 2, and in Aim 3 will assess the humoral and cell-mediated immune responses to EBV infection
in the rabbit, and whether they are comparable to key aspects of the adaptive immune response to EBV infection
in the natural host. In summary, the proposed work will inform us whether the three basic host components that
dictate EBV biology in its human host are equivalently functional in the rabbit: 1) Whether rabbit ep...

## Key facts

- **NIH application ID:** 10527462
- **Project number:** 1R21AI166197-01A1
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Clare E Sample
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $242,118
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527462

## Citation

> US National Institutes of Health, RePORTER application 10527462, A Rabbit Model of Epstein-Barr Virus Infection (1R21AI166197-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10527462. Licensed CC0.

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