# Loss of cellular identity after influenza virus infection and effects on pulmonary function

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $568,858

## Abstract

Project Summary/Abstract
Influenza viruses infect an estimated 20% of the global population every year and although infection is typically
highly acute, influenza viruses can induce prolonged changes to host pulmonary physiology. Due to their
importance for global health, influenza viruses are well studied; however relatively little work has been done
investigating the fates of infected epithelial cells. This is primarily because the dogma in the field has long held
that influenza viruses are exclusively cytopathic viruses, i.e. all infected cells are eventually killed. We were
interested in experimentally determining if any cells could survive direct viral infection and potentially continue
to affect the host after viral clearance. Using recombinant strains of influenza A virus (IAV) and influenza B
virus (IBV), along with transgenic animal systems to monitor the fates of infected cells, we found that up to 3%
of the lung epithelium is infected but is not killed by the virus or the subsequent immune response. While the
survival of some epithelial cell types was virus specific, both IAV and IBV induced the formation of populations
of “survivor” ciliated cells. Ciliated cells are a terminally differentiated cell type with a well characterized
morphology and transcriptional profile, which we hypothesized would be a powerful model to identify and
interrogate any long-term effects of viral infection on cellular physiology. We found that viral infection induced
a striking loss of the normal ciliated cell identity which not only allowed the expression of genes normally
restricted to other epithelial cell types, but also caused morphological and functional changes that were
important for the preservation of pulmonary function after infection. In this proposal, we attempt to leverage
these observations and experimental models to understand how viruses can affect cellular identity, as well as
how cellular identity flexibility relates to viral pathogenesis. The proposed experiments will reveal not only how
viral infection can break the normal rules of cellular differentiation, but also reveal a novel host adaptive
mechanism to maintain critical organ function during acute viral infection. Long term, the results of this study
may also reveal cellular processes that can be therapeutically exploited to improve the outcome of influenza
virus infection.
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## Key facts

- **NIH application ID:** 9969598
- **Project number:** 5R01HL142985-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Nicholas S Heaton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $568,858
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969598

## Citation

> US National Institutes of Health, RePORTER application 9969598, Loss of cellular identity after influenza virus infection and effects on pulmonary function (5R01HL142985-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9969598. Licensed CC0.

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