# Gammaherpesvirus miRNA suppression of EWSR1 in GC B cell infection and lymphomagenesis

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $445,184

## Abstract

Summary
The transforming human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi’s sarcoma-
associated herpesvirus (KSHV) are linked to the development of multiple types of malignancies,
including a wide range of germinal center (GC)-derived B cell lymphomas. These viruses establish
lifelong latent infections in B cells by infecting naïve B cells and driving those cells, independent
of antigen, to utilize GC reactions to proliferate and differentiate into resting memory B cells. Thus,
the transit of infected B cells through the GC is critical to gammaherpesvirus biology. Despite this,
the specific mechanisms by which gammaherpesviruses manipulate GC reactions and contribute
to GC-derived B cell lymphomas are not fully understood. Virus-encoded microRNAs (miRNAs)
are employed by gammaherpesviruses to manipulate infected cells. Importantly though, the
specific in vivo functions and biological relevance of these miRNAs are almost completely
unknown due to the strict species specificity of the human viruses. Murine gammaherpesvirus 68
(MHV68, MuHV-4) is genetically and pathogenically related to EBV and KSHV, and causes B cell
lymphomas with features of human gammaherpesvirus malignancies. We have recently
demonstrated that MHV68 miRNA miR-7-5p repression of the multifunctional host protein EWSR1
(Ewing sarcoma breakpoint protein 1) promotes latent infection of GC B cells. Notably though,
the roles of EWSR1 in both gammaherpesvirus infection and GC B cell biology are completely
unknown. In work here, we will test the hypothesis that EWSR1 repression is critical for
proliferative expansion of germinal center B cells, define the molecular mechanism by which
EWSR1 repression contributes to germinal center B cell expansion, and define the contribution
of miR-7-5p-mediated EWSR1 repression to B cell lymphomagenesis.

## Key facts

- **NIH application ID:** 10276889
- **Project number:** 1R01CA262902-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Scott A. Tibbetts
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $445,184
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276889

## Citation

> US National Institutes of Health, RePORTER application 10276889, Gammaherpesvirus miRNA suppression of EWSR1 in GC B cell infection and lymphomagenesis (1R01CA262902-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10276889. Licensed CC0.

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