# Arrhythmogenic mechanisms of acute viral myocarditis

> **NIH NIH F31** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2020 · $39,519

## Abstract

PROJECT SUMMARY
Cardiovascular disease remains the leading cause of death in the United States with up to 42% of sudden
cardiac death in young adults caused by myocarditis. Adenovirus is now recognized as a leading etiological
agent of viral myocarditis, yet our understanding of adenoviral infection in the heart is lacking due to viral host
species specificity and historical difficulty in developing model systems of cardiac infection. In all forms of heart
disease, subcellular remodeling of the cardiomyocyte occurs with disruptions in gap junction-mediated
electrical coupling known to lead to fatal arrhythmias. The primary cardiac gap junction protein, connexin43
(Cx43), is now known to have internally translated isoforms that can modulate gap junction formation and
cardiac health. Adenovirus hijacks host cell translational machinery to affect alternative translation initiation of
viral and host mRNA, and such changes would rapidly affect the cardiomyocyte proteome and therefore
electrical status of the heart. My proposed research will address gaps in the knowledge regarding mechanisms
of arrhythmogenesis during acute viral myocarditis and the contribution of alterations in translation initiation to
this process. Aim 1: Investigate arrhythmogenic mechanisms in an acute adenoviral myocarditis mouse
model. Administering MAdv3 using a retro-orbital injection in C57/B6 mice, MAdv3 DNA is found preferentially
in cardiac tissue. A mouse model will be defined for acute adenoviral myocarditis and their susceptibility to
arrhythmogenesis. Aim 2: Determine the role of altered translation initiation in adenoviral-mediated cell
junction remodeling. Many cellular junctional genes, such as Connexin 43 (Cx43), undergo alternate
translation initiation to function properly. This alternate translation initiation is impaired in disease. Adenovirus
modulates the host's translational machinery to favor alternate translation mechanisms for viral protein
synthesis by maintaining levels of host cell’s eIF2α activity. The proposed research will broaden the
understanding of how adenovirus infects the heart and causes sudden cardiac death during acute infection.
Successful completion of the work proposed will provide a new model for acute viral myocarditis and provide
insight into mechanisms of arrhythmogenesis. This proposal is significant because it will elucidate how
adenovirus infects the working heart in an adult mouse model, how the infected cell's' translational landscape
can lead to arrhythmogenesis, and it will test the potential of restoring of that landscape after infection in
protection against sudden cardiac death.

## Key facts

- **NIH application ID:** 9992908
- **Project number:** 1F31HL152649-01
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Rachel L. Padget
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,519
- **Award type:** 1
- **Project period:** 2020-04-10 → 2022-09-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992908

## Citation

> US National Institutes of Health, RePORTER application 9992908, Arrhythmogenic mechanisms of acute viral myocarditis (1F31HL152649-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9992908. Licensed CC0.

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