# Regulation of cardiomyocyte inflammation during viral infection

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $223,927

## Abstract

Project Summary / Abstract
Myocarditis is an inflammatory pathology of the myocardium, driven by both infectious and non-infectious
agents, that often precedes acute heart failure, ventricular arrhythmias, and dilated cardiomyopathies. Thus,
understanding the mechanisms that regulate its onset and resolution is crucial for the prevention and treatment
of myocardial disease. MicroRNAs are short non-coding RNAs that fine-tune inflammatory responses by post-
transcriptionally regulating immune genes. Of these, miR-208b and miR-499-5p, members of a family of
microRNAs specific to skeletal muscle and cardiac tissue (myomiRs) are aberrantly expressed in patients with
acute myocardial inflammation and predict disease severity. However, the biological significance of these
observations is poorly understood. We have previously shown that miR-208b and miR-499-5p, are aberrantly
induced by viral infection and associated antiviral cytokines in hepatocytes, where they silence both type I and
type III interferon (IFN) responses resulting in diminished viral clearance. In this study, we are proposing that
cardiomyocytes have evolved a similar mechanism to block interferon-mediated inflammation, which
cardiotropic viruses utilize to avoid immune detection and elimination. We propose that miR-208b and miR-
499-5p expression in the heart is elevated by proinflammatory injury and results in the loss of inflammatory
control and the premature resolution of crucial antiviral responses that render cardiomyocytes susceptible to
cellular death and could promote cardiac tissue damage. We propose to identify the distinct damage-
associated stimuli that regulate myomiR expression and how these coordinate inflammatory responses. We
will use unbiased approaches to identify the key molecular targets regulated by myomiRs. We will test if
myomiRs antagonize antiviral responses that leads to persistence of viral infections associated with myocardial
disease. Overall, our integrative approach will build a comprehensive gene regulatory network that
encompasses the complex interactions between microRNAs, host immune responses, tissue repair and viral
clearance in cardiac disease, from which we can discover novel molecular targets for therapeutic intervention.

## Key facts

- **NIH application ID:** 10244888
- **Project number:** 5R21AI141823-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Ram Savan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $223,927
- **Award type:** 5
- **Project period:** 2020-08-21 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244888

## Citation

> US National Institutes of Health, RePORTER application 10244888, Regulation of cardiomyocyte inflammation during viral infection (5R21AI141823-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10244888. Licensed CC0.

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