# Role of mitochondrial extracellular vesicles in CVB3 myocarditis by sex

> **NIH NIH R01** · MAYO CLINIC  JACKSONVILLE · 2022 · $747,061

## Abstract

PROJECT SUMMARY
An estimated 3.1 million cases of myocarditis/cardiomyopathy were diagnosed in 2017. 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
extracellular vesicle-like mitochondrial autophagosomes, and that CVB3 requires mitochondrial fission for viral
replication. Interestingly, other viruses that cause myocarditis have been found to use mitochondria to promote
viral replication including influenza A, HIV, poliovirus, hepatitis C virus and SARS-CoV-2. 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 cardiomyocytes induces
sex differences in cardiac inflammation during myocarditis and to determine whether microRNA and/or protein
from mitochondrial-derived extracellular vesicles influence viral replication and inflammation in a sex-specific
manner.

## Key facts

- **NIH application ID:** 10498103
- **Project number:** 1R01HL164520-01
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** DeLisa Fairweather
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $747,061
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498103

## Citation

> US National Institutes of Health, RePORTER application 10498103, Role of mitochondrial extracellular vesicles in CVB3 myocarditis by sex (1R01HL164520-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10498103. Licensed CC0.

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