# Systems Immunogenetics of Influenza Virus Infection in the Collaborative Cross

> **NIH NIH U19** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $563,507

## Abstract

Abstract: Emerging viruses, such as SARS-CoV, influenza A virus (IAV), and West Nile virus (WNV) cause
high levels of morbidity and mortality in human populations. Host immune responses can play either protective
or a pathologic role during viral infections. Therefore, understanding of the regulatory networks and signaling
pathways that determine the magnitude and quality of an individual's antiviral immune response has important
implications for human health, since these genes/pathways could be therapeutically targeted to treat virus-
induced disease, or may represent targets for enhancing the safety and efficacy of vaccines against a wide
range of viral pathogens.
Polymorphic host genes and regulatory networks have a major impact on immune response variation in human
populations. However, confounding environmental factors and/or ethical concerns limit the types of studies
that can be conducted in humans. Therefore, genetically tractable model systems that capture the range of
genetic and phenotypic diversity seen in humans, such as the Collaborative Cross (CC) are needed to
mechanistically dissect the genetics of immune variation. Our research team has quantified variation in
baseline, as well as SARS-CoV, IAV, and WNV-induced immune responses in a panel of 110 CC RIX lines
(reproducible F1 crosses between CC recombinant inbred (RI) lines that model heterozygous human
populations). To our knowledge, this represents to most comprehensive analysis of immune response variation
ever conducted in a genetic reference population, and in ongoing QTL mapping studies, we have identified
100+ quantitative trait loci (QTL) associated with variation in virus-induced innate and adaptive immunity,
inflammation and disease. Our program, which includes expertise in viral pathogenesis, innate and adaptive
immunity, and quantitative genetics will use this unprecedented data base to: 1) identify and characterize
polymorphic host genes that drive variation in virus-induced disease, 2) test how interactions between different
polymorphic genes/loci shape the host immune response, 3) test how these genes impact responses to other
viral pathogens, or function during allergy/auto-immunity, and 4) test the impact of these genes in the context
of human infections to identify targets for diagnosis, prevention and therapeutic interventions in humans.
These studies will significantly enhance our understanding of how host genetic variation shapes virus-induced
immunity and/or disease.

## Key facts

- **NIH application ID:** 10134686
- **Project number:** 3U19AI100625-08S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Mark T Heise
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $563,507
- **Award type:** 3
- **Project period:** 2020-04-16 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134686

## Citation

> US National Institutes of Health, RePORTER application 10134686, Systems Immunogenetics of Influenza Virus Infection in the Collaborative Cross (3U19AI100625-08S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10134686. Licensed CC0.

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