# Role of viral mitophagosomes in driving sex differences in myocarditis

> **NIH NIH R21** · MAYO CLINIC  JACKSONVILLE · 2020 · $122,438

## Abstract

PROJECT SUMMARY/ABSTRACT
An estimated 1.5 million cases of myocarditis were diagnosed in 2015. Patients with myocarditis are at risk of
sudden death from acute heart failure and progression to dilated cardiomyopathy, often necessitating a heart
transplant. The incidence and severity of myocarditis is higher in men than women. Additionally, there are no
disease-specific therapies to reduce myocarditis. Enteroviruses including coxsackievirus group B3 (CVB3) are
a common cause of myocarditis in the US. Viruses are frequently found in endomyocardial biopsies from
patients with myocarditis. There is currently no clear understanding of why an enterovirus like CVB3 would
target the heart or the mechanism for how a relatively mild viral infection like CVB3 leads to heart failure.
Previously it was hypothesized that an overwhelming lytic CVB3 infection damages the heart. It was recently
published that the predominant mode of viral egress for CVB3 from cardiomyocytes is in microvesicle-like
mitochondrial autophagosomes, and that CVB3 requires mitochondria for viral replication. Interestingly, other
viruses that cause myocarditis have been found to use mitochondria to promote viral replication including
influenza A, HIV, poliovirus, and hepatitis C virus. The high energy demands of cardiac muscle and abundant
mitochondria in the heart provide for the first time an explanation for why such disparate types of viruses, with
no obvious cardiac tropism, replicate in the heart. The overall goal of this proposal is to determine whether the
CVB3 replicative cycle through mitochondria in cardiac cells induces sex differences in cardiac inflammation
during myocarditis and to determine whether microRNA from mitophagosomes reduce viral replication in
mitochondria and thereby prevent heart failure during acute viral myocarditis.

## Key facts

- **NIH application ID:** 9892954
- **Project number:** 5R21AI145356-02
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** DeLisa Fairweather
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,438
- **Award type:** 5
- **Project period:** 2019-03-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892954

## Citation

> US National Institutes of Health, RePORTER application 9892954, Role of viral mitophagosomes in driving sex differences in myocarditis (5R21AI145356-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9892954. Licensed CC0.

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