# Activation of inflammatory programmed cell death by SARS-CoV-2

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2022 · $264,750

## Abstract

Project Summary
Programmed cell death is an ancient and effective defense mechanism against intracellular infection: activation
of cellular suicide in response to intracellular pathogens eliminates pathogens’ replicative niches and exposes
them to immune-mediated killing. However, when these responses occur incorrectly or overexuberantly, they
can cause tissue destruction and exacerbate inflammation. Work from many groups including our own has
shown that infection of the lung with RNA viruses can trigger cell death via the inflammatory process termed
“necroptosis.” Our preliminary data confirm that infection of cells of the lung epithelium with SARS-CoV-2 leads
to their death by necroptosis. These findings, along with additional preliminary data contained within the
proposal, lead us to hypothesize that cell death by necroptosis is a key early response to infection of the
lung with SARS-CoV-2. We further hypothesize that while a measured necroptotic response helps to
eliminate SARS-CoV-2 virus, excessive necroptosis in the lung can lead to detrimental inflammatory
pathology. We will test these hypotheses by focusing on three Aims: First, we will carry out detailed
immunological and pathological profiling of SARS-2 infected mice lacking key components of necroptotic
signaling. Next, we will use a mouse model developed in our lab to experimentally induce necroptosis in the
alveolar epithelium in conjunction with SARS-2 infection. Finally, we will use human lung slices to assess cell
death responses to SARS-2 infection in intact human tissue.

## Key facts

- **NIH application ID:** 10450286
- **Project number:** 1R21AI158230-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Andrew Atwell Oberst
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $264,750
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450286

## Citation

> US National Institutes of Health, RePORTER application 10450286, Activation of inflammatory programmed cell death by SARS-CoV-2 (1R21AI158230-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10450286. Licensed CC0.

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