# IRF-1: a brake to limit gammaherpesvirus infection and pathogenesis

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $424,117

## Abstract

PROJECT SUMMARY
Gammaherpesviruses establish life-long infection in a majority of humans worldwide and are
associated with the development of cancer, including B cell lymphomas. The intimate
relationship between gammaherpesviruses and B cell differentiation is directly linked to the
lymphomagenic capacity of these viruses. To ensure the establishment of long-term latency in
memory B cells, gammaherpesviruses drive a unique polyclonal germinal center reaction during
early infection. Germinal center reaction represents a stage of B cell differentiation that is
characterized by rapid division of activated B cells along with genetic instability driven by
enzymes that either induce DNA breaks or mutagenize DNA. It is not surprising that most
Epstein-Barr virus-driven B cell lymphomas originate from germinal center or post germinal
center B cells. This robust, gammaherpesvirus-stimulated germinal center reaction is transient
and returns to near-baseline levels in long-term infected hosts. Importantly, it is not clear what
attenuates gammaherpesvirus-driven germinal center reaction. We have identified Interferon
Regulatory Factor-1 (IRF-1) as the first host factor that specifically attenuates
gammaherpesvirus-driven germinal center reaction. Studies proposed here test the hypothesis
that IRF-1 is the critical host factor that attenuates gammaherpesvirus-driven expansion and
transformation of germinal center B cells throughout life-long infection. The proposed studies
will define IRF-1-mediated signaling changes that attenuate gammaherpesvirus-driven
expansion of germinal center response and the relative contributions of B- and T cell-intrinsic
functions of IRF-1 to this process. Further, proposed studies will develop a novel animal model
of gammaherpesvirus lymphomagenesis. Successful completion of the proposed studies will
offer insights into the tumor suppressor mechanisms of IRF-1 and generate novel animal
models that will be of value to infectious disease, immunology, and cancer fields.

## Key facts

- **NIH application ID:** 9831052
- **Project number:** 5R01CA203923-04
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Vera L. Tarakanova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $424,117
- **Award type:** 5
- **Project period:** 2016-12-05 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9831052

## Citation

> US National Institutes of Health, RePORTER application 9831052, IRF-1: a brake to limit gammaherpesvirus infection and pathogenesis (5R01CA203923-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9831052. Licensed CC0.

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