# Mechanisms and consequences of epithelial cell survival from influenza virus infection.

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $385,000

## Abstract

Project Summary
Influenza virus causes significant morbidity and mortality worldwide annually. The virus has a broad tropism for
epithelial cells in the respiratory tract. To clear the infection the immune system must confront these diverse
cells which can be harboring different levels of virus or virus antigen:MHC, have differential expression of
inhibitory ligands, and reside in different anatomical locations. To determine the long-term fate of virus infected
cells we developed a novel virus capable of permanent labeling of infected cells in reporter mice. By inserting
Cre recombinase into the virus genome, infection of mice expressing a Cre-inducible fluorophore permanently
labels the cells and allows for long-term tracking and study of infected cells. Using this tool we made the
surprising discovery that not all previously infected cells are killed by the lytic virus replication or the adaptive
immune response. We hypothesize that CD8 T cells kill or pardon infected epithelial cells depending on cell
type, the state of virus replication within the cell, and virus-induced expression of inhibitory ligands. We further
hypothesize that surviving cells are critical mediators of pulmonary recovery. Because we can visualize cells
throughout the clearance phase of infection we can exploit this system to study the epithelial cells that are
killed by CD8 T cells and the mechanisms that permit infection. The goals of this proposal are to: 1) Determine
the mechanisms of infected cell evasion from CD8 T cell-mediated killing 2) Define the roles of surviving cells
in pulmonary repair and recovery 3) Map the infected cells that are eliminated by CD8 T cells and 4) Elucidate
the mechanisms that protect and permit infection of new cells in the face of antiviral immune responses.
Importantly, the indelible labeling system employed during these studies can be extended beyond IAV, to any
virus that is amenable to foreign gene insertions. Results from this proposal will uncover fundamental
mechanisms in antiviral immunity, cellular resistance and survival, and pulmonary recovery.

## Key facts

- **NIH application ID:** 10177849
- **Project number:** 5R01AI132962-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Ryan Langlois
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2017-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177849

## Citation

> US National Institutes of Health, RePORTER application 10177849, Mechanisms and consequences of epithelial cell survival from influenza virus infection. (5R01AI132962-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10177849. Licensed CC0.

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