# EPSTEIN-BARR VIRUS EXPRESSION IN NORMAL HUMAN EPITHELIUM

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 1993 · $192,613

## Abstract

The long  term   goal of the  proposed research is to identify viral and
cellular factors, unique to human mucosa, which contribute to
Epstein-Barr virus (EBV) pathogenesis and to mechanisms of persistence.
EBV-associated diseases point to the importance of viral interactions in
human mucosa: nasopharyngeal carcinoma and oral hairy leukoplakia.
(characterized by EBV latency and an aggressively replicative infection,
respectively) are epithelial cell diseases.  African Burkitt's lymphoma,
with its unusual tissue distribution, is a malignancy of the
mucosal-associated lymphoid tissue.  Utilizing information gained in the
current grant period which suggests for the first time the existence of
multiple EBV variants with distinct biologic differences and tissue
tropisms, we propose the following aims to reach our long-term goals: 1)
Determination of the molecular structure of lytic EBV; 2) Evaluation of
the distribution of transforming and lytic variants within epithelial and
lymphoid components of the mucosal system; 3) Elucidation of mechanisms
for EBV persistence in the epithelial components of the mucosa.
     Based on the known biologic activity of a spontaneous laboratory
mutant deleted for the EBV nuclear antigen 2 (EBNA2) encoding gene, we
postulate that similar wild type variants represent the "missing link' in
our understanding of EBV pathogenic mechanisms.  By molecular cloning and
polymerase chain reaction analysis, we will delineate (under aim 1) the
genetic structure of EBNA2 deleted virus taken directly from throat
washings, thus avoiding the selection bias inherent with passage in
lymphocyte culture.  Demonstration of deletions and potential gene
rearrangements will provide an indication of altered biologic activity.
In aim #2, use of select genotypic markers amenable to PCR analysis will
allow us to track EBV variants through tissue compartments of the mucosal
system, identify tissue tropisms, and locate sites for potential
interaction between strains.  Finally, we will use EBV strains, isogenic
except for their EBNA2 gene, to analyze in experimentally infected
epithelium transcription from EBV's putative transforming genes.  In
infected human epithelial cell implants maintained in nude mice, we will
relate patterns of gene expression to the EBNA2 deletion mutant's ability
to sustain long-term infection in the absence of a viable B cell
component.

## Key facts

- **NIH application ID:** 3177274
- **Project number:** 5R01CA038877-09
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **SAM.gov UEI:** JL4JHE9SDRR3
- **Principal Investigator:** JOHN W SIXBEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $192,613
- **Award type:** 5
- **Project period:** 1984-12-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177274

## Citation

> US National Institutes of Health, RePORTER application 3177274, EPSTEIN-BARR VIRUS EXPRESSION IN NORMAL HUMAN EPITHELIUM (5R01CA038877-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177274. Licensed CC0.

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