# Using the Collaborative Cross to discover immunoregulatory mechanisms that control WNV infection

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $220,625

## Abstract

West Nile virus (WNV) is a mosquito-transmitted flavivirus that causes severe neurological disease is humans
and other animals. WNV recently emerged in the USA and continues its spread in the Americas, thus placing
millions of people at risk of infection, development of neurologic disease, and death. The host immune processes
that control WNV infection are not fully understood. The innate immune response against WNV is critical for
controlling infection, and has been modeled in traditional inbred mouse lines but these inbred models lack the
genetic diversity present in human populations and thus are limited in their ability to evaluate the full range of
WNV disease and immune outcomes. We have therefore evaluated WNV disease susceptibility and host innate
immune responses to WNV infection in the Collaborative Cross (CC) model. Our studies show that unlike inbred
mouse populations, the CC captures the full range of WNV pathogenesis and outcomes observed in humans.
Our preliminary studies have now identified unique quantitative trait loci (QTL) encoding host genes that are
linked to immune-regulatory phenotypes of WNV control. Thus, we will conduct the following Aims to: 1) Apply
the CC to identify gene(s) regulating peripheral viral control in the spleen, and 2) define novel virus stimulated
genes (VSG) in the CC that control neuroinvasion and neuropathogenesis of WNV infection.

## Key facts

- **NIH application ID:** 9957014
- **Project number:** 5R21AI145359-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Michael Gale
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $220,625
- **Award type:** 5
- **Project period:** 2019-06-17 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957014

## Citation

> US National Institutes of Health, RePORTER application 9957014, Using the Collaborative Cross to discover immunoregulatory mechanisms that control WNV infection (5R21AI145359-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9957014. Licensed CC0.

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