# Innate Immune Function in Influenza-Associated Myopathy

> **NIH NIH P20** · UNIVERSITY OF MAINE ORONO · 2024 · $270,911

## Abstract

PROJECT SUMMARY / ABSTRACT
Skeletal muscle myopathy has been reported following infection by influenza virus. In Influenza-Associated
Myopathy (IAM), a systemic influenza infection can result in acute skeletal muscle damage that ranges from non-
specific degeneration to extensive necrosis. IAM is associated with high serum creatine kinase (CK) levels.
During the 2009 H1N1 influenza epidemic, 62% of hospitalized patients had increased serum CK levels. Given
that an estimated 9-45 million individuals acquire influenza infections annually in the US, developing new
strategies to reduce muscle damage are needed as influenza vaccines are difficult to design because of
unpredictable changes in viral strains within and across populations. The severity of viral disease varies between
individuals and depends on how the immune system responds to infection. One roadblock to understanding the
pathogenesis of IAM is that the relative contributions of the virus and host factors in vivo are not well understood.
Biopsy studies cannot show the temporal dynamics of viral invasion and subsequent recruitment of neutrophils
and macrophages into muscle. The zebrafish is a powerful model to study host-pathogen interactions as genetic
tools can be combined with in vivo imaging of transparent embryos. My laboratory uses a recently-developed
zebrafish model of influenza A virus (IAV) infection where it was shown that: 1) IAV-infected zebrafish embryos
exhibited mild muscle degeneration with sarcolemma damage and compromised extracellular matrix (ECM)
adhesion; and 2) neutrophils localize to sites of muscle damage in IAV-infected embryos. Our specific goal in
this proposal is to determine the mechanisms through which neutrophils influence the pathology of IAM. This
project will test the novel hypothesis that overactivation of neutrophils during IAV infection triggers a damaging
hyperinflammatory response that contributes to myopathy. In the first aim, we will test the hypothesis that
reduction in reactive oxidative species (ROS) production following IAV infection will limit damage by
strengthening muscle cell-ECM adhesion, and increase survival. This will be accomplished by examining how
global ROS reduction and neutrophil-specific ROS reduction alters muscle degeneration, cell-ECM adhesion,
and neutrophil localization in the muscle in vivo using IAV multi-spectral fluorescent reporter (Color-flu) strains.
In the second aim, we will test the hypothesis that defects in neutrophil migration following IAV infection will
increase muscle degeneration, and weaken ECM adhesion. To accomplish this, we will use in vivo confocal
imaging to study two zebrafish mutants with defective neutrophil migration infected with Color-flu to test our
hypotheses that: 1) neutrophil invasion into skeletal muscle is reduced, and 2) muscle degeneration is increased
and cell-ECM adhesion is increased over controls. One of these mutants overexpresses miR-199 in neutrophils
that disrupts neutrophil migr...

## Key facts

- **NIH application ID:** 10821305
- **Project number:** 5P20GM144265-02
- **Recipient organization:** UNIVERSITY OF MAINE ORONO
- **Principal Investigator:** Benjamin L King
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $270,911
- **Award type:** 5
- **Project period:** 2023-04-05 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821305

## Citation

> US National Institutes of Health, RePORTER application 10821305, Innate Immune Function in Influenza-Associated Myopathy (5P20GM144265-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10821305. Licensed CC0.

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