# From friend to foe: proviral role of IRF-3 in chronic gammaherpesvirus infection

> **NIH NIH R21** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $248,517

## Abstract

Abstract
Gammaherpesviruses establish life-long infections in >95% of adults worldwide and are
associated with B cell lymphomas. Gammaherpesvirus-driven cancers develop in both
immunocompromised and immunocompetent individuals; prevention of such cancers is
currently impossible due to absence of vaccines, curative antivirals, and defined risk factors for
lymphomagenesis. Manipulation of B cell differentiation lies at the heart of chronic
gammaherpesvirus infection and pathogenesis. Specifically, gammaherpesviruses use natural
proliferative capacity of germinal center B cells to amplify latent viral reservoir. Further,
germinal center B cells are believed to be the target of viral transformation, as a majority of
gammaherpesvirus-driven B cell lymphomas are germinal center-derived. Despite the
importance of germinal center response for chronic infection and lymphomagenesis, very few
factors that control infection of germinal center B cells have been defined. Interferon Regulatory
Factor 3 (IRF-3) is a transcription factor that targets many cellular genes, including interferon
(IFN) β. We discovered that, contrary to the predicted role of IRF-3 as an antiviral factor, IRF-3
supports latent gammaherpesvirus infection of germinal center B cells. The proposed studies
test the hypothesis that IRF-3 is usurped by gammaherpesvirus to facilitate latent infection of
germinal center B cells, with subsequent generation of memory B cells that host life-long latent
viral reservoir. This is achieved through IRF-3-dependent regulation of cellular and viral target
genes. Successful completion of the proposed studies will offer an insight into the mechanism
by which the virus usurps a classical innate antiviral factor for the viral benefit.

## Key facts

- **NIH application ID:** 10868272
- **Project number:** 1R21AI182596-01
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Vera L. Tarakanova
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $248,517
- **Award type:** 1
- **Project period:** 2024-01-19 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868272

## Citation

> US National Institutes of Health, RePORTER application 10868272, From friend to foe: proviral role of IRF-3 in chronic gammaherpesvirus infection (1R21AI182596-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10868272. Licensed CC0.

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