# Epstein-Barr Virus Entry into Epithelial Cells

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2024 · $234,895

## Abstract

Project Summary/Abstract:
Epstein-Barr virus (EBV) is a-herpesvirus that is ubiquitous in humans and infects epithelial cells and B cells.
EBV typically causes mononucleosis in humans but is also oncogenic and is associated with a wide array of
malignancies in humans including Burkitt lymphoma, Hodgkin Lymphoma, nasopharyngeal carcinoma (NPC),
and gastric carcinoma. Recently we identified ephrin receptor tyrosine kinase A2 (EphA2), which binds the EBV
encoded gH/gL, as the EBV epithelial entry receptor. EphA2 is a transmembrane receptor tyrosine kinase that
functions in the regulation of cell growth, survival, angiogenesis, and migration. It is expressed in adult epithelial
tissue such as gastric and oral epithelium. However, more recent studies and our data have shown that EphA2
may not be accessible in healthy epithelium for EBV infection. This indicates that EBV infection of the epithelium
is a complicated process that has not been fully elucidated. In our proposed studies, we will investigate the
mechanism of EBV infection of the epithelium using the Longnecker Laboratory's experience studying the
mechanism of Herpes Simplex Virus (HSV) epithelial infection and studying EBV B cell and epithelial cell
infection. For this proposal, in Aim 1, we intend to study the role of tight junctions in protecting normal epithelium
from EBV infection. We also plan to study whether LPS derived from Helicobacter pylori (HP) plays a role in
breaking tight junctions facilitating EBV infection since HP is considered a primary carcinogen in gastric cancer
pathogenesis. In Aim 2, we will investigate whether polymorphisms in EphA2 have different affinities in binding
to EBV gH/gL, signaling through EphA2 which may result in differences in the breakdown of TJs and altering
EBV infection. In Aim 3, since inflammatory conditions such as gastritis and HP infection may increase the risk
of for gastric cancer, we hypothesized that these conditions induce the expression of other receptor(s) or
co-receptor(s) that aide in the entry of virus into healthy epithelium. When we compared gene expression in HP
infected AGS cells and HP infected gastric tissue with that in control AGS cells or tissue without HP infection.
We found 15 potential genes which are membranes proteins that were upregulated in HP infected cells. We
plan to investigate if the encoded proteins regulate EBV infection positively or negatively. By investigating the
mechanism how EBV entry into epithelial cells, we will better understand the viral-host interactions, cellular
factors, and role of tissue damage, and inflammation in EBV infection of epithelial cells which will aide in
development of novel treatments and prevention strategies EBV-related epithelial pathologies.

## Key facts

- **NIH application ID:** 10805862
- **Project number:** 1R21AI175798-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Richard M Longnecker
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $234,895
- **Award type:** 1
- **Project period:** 2024-06-03 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805862

## Citation

> US National Institutes of Health, RePORTER application 10805862, Epstein-Barr Virus Entry into Epithelial Cells (1R21AI175798-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10805862. Licensed CC0.

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