Ohio State to test a “master regulator” to prevent viral-induced heart failure
A new study at The Ohio State University College of Medicine could lay the groundwork for the development of new therapies in the treatment and prevention of heart failure caused by viral infection, the most common cause of the disease and the deadliest. Supported by a $2.3 million grant from the National Heart, Lung and Blood Institute, the study aims to explain the mechanisms involved in the heart’s immune response to viral infection and test a protein that could hold the key to stopping the infection before it can injure the heart muscle and do further damage to the body.
The protein–BEX1 (brain expressed X-linked 1)–offers great promise as a “master regulator” in controlling the level of pro-inflammatory mRNAs and preventing excessive inflammatory response in the heart’s fight against viral infection.
“Before we can find new therapies to treat or prevent virus-induced heart failure, we must first understand the mechanisms involved in the heart’s immune defense response,” says Federica Accornero, PhD, associate professor of Physiology and Cell Biology, and lead investigator in the study. “Preliminary data have led us to the hypothesis that BEX1 plays an antiviral role by regulating a protein called EPRS (glutamyl-prolyl-tRNA synthetase).”
The heart defends itself against an invading virus by initiating an immune response that involves recruiting inflammatory cells to fight the invasion and prevent its spread. Inflammation is essential for a successful antiviral response, but excessive inflammation can cause harm to the myocardium during infection.
“The heart must carefully ‘tune’ inflammation to prevent viral proliferation, while avoiding the harm caused by excessive inflammation,” says Dr. Accornero. “Understanding the factors involved in ‘tuning’ the heart’s inflammatory response is necessary in order for new therapeutics for cardiac viral infection to be developed.”
Evaluating this hypothesis and elucidating the role of BEX1 in immunity and inflammation, the study hopes to (1) determine the effect of BEX1 on cardiotropic viral infection in vivo; (2) determine the contribution of BEX1 to antiviral gene programs in the heart; and (3) elucidate the mechanism by which BEX1 regulates antiviral responses.
The study is co-lead by Jacob Yount, PhD, professor of Microbial Infection and Immunity, and co-director of the Viruses and Emerging Pathogens Program at Ohio State’s Infectious Diseases Institute. The institute’s work in elucidating the molecular mechanisms by which certain proteins inhibit infection is advancing our understanding of immune responses and infection defense strategies.
The Accornero and Yount laboratories form a synergistic team to address vital questions regarding how cardiotropic viruses induce inflammation, fibrosis and dysfunction in the heart. Dr. Accornero provides extensive academic experience in studying causes and treatments for heart failure and is the discoverer of BEX1 involvement in cardiac inflammation. Dr. Yount provides virology and viral immunology expertise, developing models of cardiac infection and recently publishing the first mouse model of cardiac complications from the human influenza A virus. This powerful collaboration will result in fundamental new insights into cardiac infection biology that may ultimately be manipulated for heart failure treatment or prevention.