# INFECTION OF B LYMPHOCYTES BY EPSTEIN BARR VIRUS

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1991 · $210,811

## Abstract

Epstein-Barr virus (EBV), a human herpesvirus, is a significant
human pathogen.  It is a candidate human cancer virus as it is
strongly linked to nasopharyngeal carcinoma and Burkitt's
lymphoma, two malignancies and it is oncogenic in subhuman
primates.  In vitro, EBV transforms human B lymphocytes thereby
generating permanent polyclonal cell lines.  EBV is the etiologic
agent of infectious mononucleosis, a self-limited
lymphoproliferative disease which represents a significant health
hazard in immunocompromised individuals; it is also associated
with human autoimmune diseases.  EBV reactivation frequently
occurs during AIDS.

Although the entire EBV genome has been molecularly cloned and
knowledge of genetic features which lead to transformation is
rapidly accumulating, little is known of the viral and cellular
factors which permit this virus to infect B lymphocytes and
epithelial cells.  The primary objective of this proposal is the
understanding, on a molecular and biochemical level, of the early
events involved in EBV infection of human cells.  EBV receptor
(CR2) expression in B lymphocytes will b down-regulated by B cell
activation and by transfection with vectors encoding anti-sense
CR2 mRNA.  CR2 will be introduced into various eucaryotic cells
which lack endogenous CR2 by transfection of CR2 cDNA.  The
consequences of such altered CR2 expression including ability to
bind and internalize EBV and C3dg and susceptibility to EBV
induced B cell activation and transformation will be ascertained.
The role of CR2 in EBV infection of epithelial cells will also be
addressed.  Primary epithelial cell cultures and epithelial cell
lines will be examined for CR2 and EBV expression by in situ
hybridization with high specific activity 35S-labeled RNA or DNA
probes.

Another primary goal of this project is the elucidation of the
structure of CR2 and its various functional and structural
domains.  These studies will be aided by the recent isolation of a
full-length CR2 cDNA clone and will be supplemented by the use
of proteolytic and chemically cleaved CR2 fragments and
synthetic peptides representing functionally important portions of
the molecule.  Similar studies of the functionally relevant regions
of EBV gp350 and C3dg, the CR2 ligands, are planned.  These data
will be used for formulate models for the CR2/EBV receptor
ligand complexes.  Physicochemical approaches and potentially x-
ray crystallography will be used to test these models.  These
planned studies will reveal basic knowledge about virus-host cell
interactions in a model system of human disease and they may
potentially provide rationales for blocking the early stages of EBV
infection.

## Key facts

- **NIH application ID:** 3173725
- **Project number:** 5R01CA036204-07
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **SAM.gov UEI:** PHZJFZ32NKH4
- **Principal Investigator:** Glen R Nemerow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $210,811
- **Award type:** 5
- **Project period:** 1985-04-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173725

## Citation

> US National Institutes of Health, RePORTER application 3173725, INFECTION OF B LYMPHOCYTES BY EPSTEIN BARR VIRUS (5R01CA036204-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173725. Licensed CC0.

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