# Development of an influenza A virus and Aspergillus fumigatus coinfection model

> **NIH NIH R21** · DARTMOUTH COLLEGE · 2021 · $205,000

## Abstract

ABSTRACT
Influenza A virus (IAV) infected patients admitted to the ICU face severe secondary infection
complications. There is increasingly strong evidence that secondary fungal infections with Aspergillus
fumigatus (Af) present a significant risk for ICU patients with severe IAV infection. Overall,
approximately 20% of severe IAV patients in the ICU may develop secondary Af infection. Currently,
there is a critical gap in understanding how and why these fungal secondary infections develop
in IAV patients. This R21 application aims to fill this gap by generating a robust small animal IAV-Af
coinfection model that can be used to dissect the molecular mechanism(s) by which IAV infection
increases susceptibility to Af challenge. Our initial pilot experiments demonstrate that IAV infection four
days prior to Af challenge results in significant fungal growth and tissue invasion, which is absent in
naïve mice challenged with Af. In SA1 of this R21 proposal we will further optimize and develop this
IAV-Af coinfection model to ensure it is highly reproducible and define the importance of IAV serotype
and Af clinical strain heterogeneity in susceptibility to coinfection. In SA2, we will test the hypothesis
that IAV infection impairs pulmonary leukocyte anti-fungal activity using two innovative techniques: 1)
Fluorescent Aspergillus reporter (FLARE) strains to directly quantify anti-fungal activity of leukocyte
populations at a cell single level and 2) Single cell RNA sequencing (scRNA-Seq) to monitor
transcriptional changes in pulmonary leukocyte populations in an unbiased manner. These data will
provide the first insights into mechanisms driving Af susceptibility following IAV infection. Overall, this
research fills a critical gap by providing the field with a unique and highly needed IAV-Af coinfection
model and provides a unique and robust dataset for the development of future focused, mechanistic
R01 applications.

## Key facts

- **NIH application ID:** 10089411
- **Project number:** 5R21AI152019-02
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** JOSHUA J OBAR
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,000
- **Award type:** 5
- **Project period:** 2020-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089411

## Citation

> US National Institutes of Health, RePORTER application 10089411, Development of an influenza A virus and Aspergillus fumigatus coinfection model (5R21AI152019-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10089411. Licensed CC0.

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