# CLONAL VIRULENCE FEATURES OF THE EBV TERMINAL REGION

> **NIH NIH R01** · NORTH SHORE UNIVERSITY HOSPITAL · 1987 · $96,632

## Abstract

In the present funding period, we observed that the terminal
regions of intracellular Epstein-Barr virus (EBV) genome exhibit
marked variation in their restriction-fragment profile in
individual, isogenic B-cell lineages cloned directly from three
patients.  Furthermore, we found that the clonotypic arrays of
EBV terminal-region restriction fragments are maintained
relatively stably, during in vivo and in vitro proliferation of EBV-
transformed cell lineages.  The most important implications of
these findings are explored here, as follows.

First, EBV terminal-fragment analysis can be used to help
determine whether EBV infects the progenitor cell of tumor-cell
populations, or whether it secondarily infects the tumor
population after initial proliferation and dissemination (the
"passenger virus" notion).  Here, we propose to analyze the EBV
terminal-region fragment in tumor specimens of nasopharyngeal
carcinoma, African Burkitt Lymphoma, and AIDS-related B-
lymphomas to answer this question.

Second, our findings suggest one mechanism of the clonal
dominance observed in EBV-related malignancies.  The viral gene
encoding an important 'early' transmembrane protein
(IMP/LYDMA) has been localized by others to a site within about
0.6 kb of the EBV terminal-repeats.  The IMP/LYDMA gene
product is thought to be important in immune recognition of EBV-
infected cells, and possibly in cell transformation.  We suggest
that the clonal heterogeneity observed in the DNA of intracellular
viral terminal regions is associated with cis-acting effects on
IMP/LYDMA transcription; evidence provided here indeed
indicates clonal variation in IMP/LYDMA transcription.  We
propose to further analyze the structure and function of
intracellular EBV terminal regions.  First, the nature and location
of clonal heterogeneity of terminal-region DNA will be further
analyzed in our cell clones in tumor tissues.  Second, quantitative
estimates of clonal transcription of IMP/LYDMA will be obtained.
Third, clonal variation in the chromatin structure of intracellular
EBV terminal regions will be studied.  Finally, members of one set
of isogenic cell clones will be tested for their individual
susceptibility to killing by autologous effector cells, in
cytotoxicity assays; and these results will be correlated with the
quantitative estimates of clonal transcription of IMP/LYDMA.
The proposed studies utilize current findings to discern features
of the EBV-terminal region which may be important in clonal
dominance and tumorigenesis induced by EBV.

## Key facts

- **NIH application ID:** 3173123
- **Project number:** 7R01CA035536-05
- **Recipient organization:** NORTH SHORE UNIVERSITY HOSPITAL
- **Principal Investigator:** Nathaniel A. Brown
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $96,632
- **Award type:** 7
- **Project period:** 1987-09-01 → 1990-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173123

## Citation

> US National Institutes of Health, RePORTER application 3173123, CLONAL VIRULENCE FEATURES OF THE EBV TERMINAL REGION (7R01CA035536-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173123. Licensed CC0.

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