# Live imaging of SARS-CoV-2 infection in novel humanized mice

> **NIH NIH R24** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $499,998

## Abstract

PROJECT SUMMARY
The SARS-CoV-2 pandemic is an unprecedented challenge for the global health community, and there is
urgent need to understand the pathogenesis of SARS-CoV-2 and emerging viral variants. The pathology
associated with SARS-CoV-2 infection ranges from asymptomatic to severe, in some cases fatal disease that
correlates with inflammatory cell death during infection, activation of the immune system and release of
inflammatory cytokines or a “cytokine storm”. Unfortunately, available animal models of SARS-CoV-2 infection
do not fully recapitulate the human immune response to viral infection due to multiple differences in genomes,
molecular and metabolic pathways, and immune system regulation. The goal of our supplemental proposal in
response to PA-20-272 is use a panel of translational humanized mouse models developed by Dr. Leonard
Shultz at The Jackson Laboratory to study the clearance of SARS-CoV-2 and the variants that are continually
emerging, and for the testing of human-specific therapies that will mitigate the pathology associated with
COVID-19. In addition, we will use a novel in vivo bioluminescence imaging approach to monitor the kinetics of
SARS-CoV-2 spread and clearance in real time in vivo. We have assembled a team of investigators with
extensive experience in 1) creating new humanized mouse strains (Dr. Leonard Shultz at The Jackson
Laboratory), 2) engrafting human immune systems into immunodeficient mice (Drs. Dale Greiner and Michael
Brehm at UMass), 3) the study of human viral pathogens (Dr. Priti Kumar at Yale University), and 4) expertise
in imaging virus infection in real time in vivo (Dr. Pradeep Uchil at Yale University). We will leverage the
resources of The Jackson Laboratory to facilitate the rapid distribution of effective models to the scientific
community, uniquely positioning our group to contribute quickly to the knowledge of SARS-CoV-2 biology. Dr.
Shultz has generated new models of NSG mice expressing human ACE2 and will provide these mice to Dr.
Kumar and to Drs. Brehm and Greiner. Drs. Brehm and Greiner will engraft the mice with human UCB CD34+
HSCs and will provide engrafted mice to Dr. Kumar’s laboratory. Drs. Kumar and Uchil will perform the
infection studies with SARS-CoV-2 and its variants in both non-human immune engrafted (Specific Aim 1) and
human immune engrafted mice (Specific Aim 2) and analyze the kinetics of virus clearance in real time using
novel bioluminescent imaging technology. In addition, overall mouse health, viral load in tissues and
inflammatory cytokines will be monitored. We will validate the optimal SARS-CoV-2 infection protocols with the
NSG mouse stocks. Ultimately, these studies will determine the clearance and pathogenesis of SARS-CoV-2
and variants in the absence or presence of a human immune system.

## Key facts

- **NIH application ID:** 10400392
- **Project number:** 3R24OD026440-03S1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Michael Allen Brehm
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $499,998
- **Award type:** 3
- **Project period:** 2019-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400392

## Citation

> US National Institutes of Health, RePORTER application 10400392, Live imaging of SARS-CoV-2 infection in novel humanized mice (3R24OD026440-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10400392. Licensed CC0.

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