# Mechanistic characterization of a new master regulator of cardiac virus infections

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $581,395

## Abstract

Project Summary
Cardiac viral infection is a common cause of heart failure for which therapeutics are lacking. Viruses primarily
damage the heart by directly lysing host cells and causing widespread necrosis. The heart responds to
infection by recruiting inflammatory cells to fight and prevent the spread of the virus. Inflammation is essential
for a successful antiviral response, but excessive inflammation can cause a net harm to the myocardium during
infection. The heart must carefully tune inflammation to prevent viral proliferation while avoiding the harm
caused by excessive inflammation. Understanding the factors involved in tuning the heart's inflammatory
response will be necessary to develop therapeutics for cardiac viral infection. We discovered that a protein
called BEX1 (brain expressed X-linked 1) serves a pro-inflammatory role in the heart during sterile injury. We
have also found that BEX1 acts in cardiomyocytes as part of a ribonucleoprotein complex regulating the level
of pro-inflammatory mRNAs. Nevertheless, the direct mechanism by which BEX1 regulates cardiac
inflammation has not been elucidated, and it is not known if BEX1 regulates the heart's response to virus
infections. In this proposal we seek to understand BEX1's role in the response of the heart to viruses with the
following aims: 1) To determine the effect of BEX1 on cardiotropic viral infection in vivo; 2) To determine the
contribution of BEX1 to antiviral gene programs in the heart; and 3) To elucidate the mechanism by which
BEX1 regulates antiviral responses. Preliminary data have led us to the hypothesis that BEX1 plays an antiviral
role by regulating a protein called EPRS (glutamyl-prolyl-tRNA synthetase). Evaluating this hypothesis and
elucidating the role of BEX1 in immunity and inflammation will be necessary to gain a better understanding of
viral infection and inflammatory diseases, and could lead to the discovery of valuable therapeutic targets.

## Key facts

- **NIH application ID:** 10045127
- **Project number:** 1R01HL154001-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Federica Accornero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $581,395
- **Award type:** 1
- **Project period:** 2020-09-08 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045127

## Citation

> US National Institutes of Health, RePORTER application 10045127, Mechanistic characterization of a new master regulator of cardiac virus infections (1R01HL154001-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10045127. Licensed CC0.

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