# Determining the impact of stromal cell-mediated type I IFN signaling on alphavirus pathogenesis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $597,002

## Abstract

ABSTRACT
 Type I interferons (IFNs) are important innate cytokines that influence local and systemic
immune responses. They can play beneficial roles through their antiviral properties and ability to
augment host immune responses; however, IFN responses can also have detrimental outcomes
for the host. The factors that determine these differential outcomes are poorly understood.
 Chikungunya virus (CHIKV) is a re-emerging alphavirus that causes severe, febrile arthritis
and myositis. Type I IFNs are a key host response during alphavirus infection. Mice lacking the
type I IFN receptor develop severe and rapidly fatal disease following infection with CHIKV or
other alphaviruses. In studying this response, we have made several interesting observations.
First, IFNs exert both beneficial and detrimental effects during CHIKV infection. Second, IFNs
regulate the host response to CHIVK by signaling on non-hematopoietic cells, likely stromal cells
and other structural cells such as fibroblasts and endothelial cells. The contribution of stromal
cells to in vivo host immune responses remains poorly defined, even though these cell types are
among the first cells to respond to vaccinations and vector-borne infectious diseases.
 Our proposed research will test the hypothesis that type I IFNs play distinct roles throughout
the course of CHIKV infection due to the responses of distinct stromal cell populations. The
studies proposed will utilize mouse genetics to conditionally delete IFN signaling from different
stromal cells, temporal antibody blocking strategies, and RNA sequencing techniques to
interrogate how IFNs impact these specific cells at different times during CHIKV infection. These
findings have the potential to greatly expand our understanding of stromal cells IFN responses
and how these cells contribute to shaping the tissue-specific immune response during infections
and vaccinations.

## Key facts

- **NIH application ID:** 10979917
- **Project number:** 1R01AI179890-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Deborah J Lenschow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $597,002
- **Award type:** 1
- **Project period:** 2024-06-13 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979917

## Citation

> US National Institutes of Health, RePORTER application 10979917, Determining the impact of stromal cell-mediated type I IFN signaling on alphavirus pathogenesis (1R01AI179890-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10979917. Licensed CC0.

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