# Systems Immunogenetics of Emerging Coronavirus Infections in the Collaborative Cross

> **NIH NIH U19** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $412,634

## Abstract

SARS-CoV-2 is causing an unprecedented pandemic that is likely to result in millions of deaths, with devastating
economic and public health consequences. Approximately 10% of SARS-CoV-2 infections result in COVID-19
pneumonia that progresses to acute respiratory distress syndrome (ARDS). A growing body of evidence
suggests that the host inflammatory response plays a major role in driving severe disease outcomes. Therefore,
it is essential to understand how SARS-CoV-2 interacts with the host inflammatory response to drive COVID-19
pathogenesis. Recent studies suggest that bats, which are the natural reservoir of group 2b coronaviruses like
SARS-CoV-2, have dampened NLRP3 function, which may allow these viruses to infect bats without causing
serious disease. This indicates that NLRP3 or other NLR inflammasomes, may play an important role in SARS-CoV-2-induced inflammation and thereby drive virus-induced respiratory pathology. Given that these genes and
pathways are also polymorphic in humans, this raises the possibility that genetic variation in NLR gene networks
may contribute to variation in SARS-CoV-2 susceptibility. Therefore, we propose to take advantage of our
research team’s unique capabilities in SARS-CoV-2 pathogenesis and mouse genetics to directly test whether
NLRP3 or other NLR inflammasome pathways contribute to SARS-CoV2-induced disease. We will also test
whether genetic variation in these pathways affects disease outcome or virus-induced immunity. This effort will
be further enhanced by a collaboration with Drs. Gary Nolan and Richard Ulevitch (U19AI100627), which will
allow us to test whether these genes/pathways are activated during SARS-CoV-2 infection in humans. Therefore,
the proposed studies, which fall within the scope or the parent grant U19AI100625, achieve three critical research
goals by: 1) testing the role of NLRP3 and related pathways in driving SARS-CoV-2 disease pathogenesis, 2)
testing whether genetic variation in these pathways affects SARS-CoV-2-induced inflammatory responses or
adaptive immunity, and 3) developing novel mouse models that reproduce key features of COVID-19 disease
pathogenesis and inflammation.

## Key facts

- **NIH application ID:** 10240845
- **Project number:** 3U19AI100625-09S2
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Ralph S Baric
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,634
- **Award type:** 3
- **Project period:** 2020-06-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240845

## Citation

> US National Institutes of Health, RePORTER application 10240845, Systems Immunogenetics of Emerging Coronavirus Infections in the Collaborative Cross (3U19AI100625-09S2). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10240845. Licensed CC0.

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