# Not just acute: IRF-7 has two site-specific functions against chronic gammaherpesvirus infection

> **NIH NIH F31** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $1

## Abstract

Proposal Summary
Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections and are defined by distinct
lytic and latent lifecycles. Importantly, human gammaherpesviruses promote a variety of cancers in both
immunocompetent and immunocompromised hosts. While risk factors for these virus-driven cancers are poorly
understood, it is clear that robust virus-driven germinal center expansion, as well as reactivation of the virus
from latency precedes viral oncogenesis. Therefore, host factors that restrict these two processes during
infection may represent potential therapeutic targets.
Due to the high prevalence and tremendous species specificity of human gammaherpesviruses, the mouse
pathogen murine herpesvirus 68 (MHV68) is widely utilized as the small animal model of gammaherpesvirus
pathogenesis. A particular strength of this model is the ability to genetically modify the host to examine the
cellular and molecular mechanism by which infection is controlled. With this model we have recently identified
new and exciting function of the previously underappreciated host factor IRF-7 during gammaherpesvirus
infection. Specifically, we found that IRF-7 restricts gammaherpesvirus-driven germinal center expansion at 16
days post infection. Additionally, we found that in the absence of IRF-7, MHV68 reactivates to a greater
frequency from peritoneal cells compared to WT. This phenotype was not observed in the spleen. We
hypothesize that IRF-7 mediates independent antiviral functions in two separate sites within the host.
The in vivo experiments proposed here will provide an extensive, yet focused analysis of the cellular and
molecular importance of IRF-7 expression in both the spleen and peritoneal cavity of the host during
gammaherpesvirus infection. Importantly, successful completion of these studies will provide insight into the
control of gammaherpesvirus infections, which would offer potential therapeutic targets for infected individuals
particularly susceptible to the associated oncogenic effects of gammaherpesviruses.

## Key facts

- **NIH application ID:** 9979627
- **Project number:** 5F31CA243364-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Kaitlin E Johnson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2019-07-11 → 2020-07-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979627

## Citation

> US National Institutes of Health, RePORTER application 9979627, Not just acute: IRF-7 has two site-specific functions against chronic gammaherpesvirus infection (5F31CA243364-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9979627. Licensed CC0.

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