UVA study uncovers key heart responses to viral infection

Researchers at the University of Virginia have made a significant discovery that could change how doctors treat viral infections of the heart. The study, published in Science Advances, reveals that the heart responds to viral infections in one of three distinct ways, offering new insights that may lead to better treatments for people at risk of heart failure. These findings bring new hope for patients dealing with viral myocarditis, a condition that can silently damage the heart.

Understanding Viral Myocarditis: A Critical Challenge 

Viral myocarditis occurs when a virus infects the heart muscle, leading to inflammation and potentially severe complications. Often undiagnosed until heart function deteriorates, it is a leading cause of sudden cardiac death in young adults and athletes, and a major contributor to dilated cardiomyopathy, a form of heart failure. Despite its prevalence, there are currently no targeted treatments to address viral infections in the heart, making it a pressing issue for researchers and clinicians.

The research team, led by Kevin Janes, John Marshall Money Professor in UVA's Departments of Biomedical Engineering and Biochemistry & Molecular Genetics, analyzed RNA sequencing data from nearly 1,000 human heart samples. They found that about 20% of the hearts showed molecular signs of viral infections, even though the people didn’t have any symptoms.

The researchers used advanced bioinformatics and computational models to scan the genetic information from each heart and look for specific patterns in how genes were altered. They compared the genetic activity in infected hearts to healthy ones, identifying which genes were turned on or off during an infection. 

“By grouping hearts with similar gene activity, we uncovered three clear patterns in how the heart reacts to a viral infection,” said Janes. “The analysis suggested which responses were helping the heart to heal and which were causing more damage.”

Three Ways the Heart Adapts to Viral Infections 

The study highlighted three key ways the heart reacts to viral infections:

1. Inflammatory Response: The heart goes into overdrive to fight off the infection, causing inflammation that can damage heart tissue and is often linked to heart failure.
2. Adaptive Recovery: In this more favorable response, the heart adapts to the viral stress without causing damage, effectively coping with the infection.
3. Exhaustion Phase: In this state, the heart's ability to respond weakens over time, possibly increasing the risk of heart failure.

These patterns were observed in all virus-infected hearts, regardless of the virus type, suggesting a common set of heart responses to infections that could be targeted with future therapies.

“Understanding how the heart copes with viral infections will set the stage for new therapeutic strategies to prevent infections from progressing to heart failure,” Janes said. 

Implications for Treatment 

“Our results provide a map for how the heart adapts to viral stress,” said Cameron Griffiths, lead author of the study and a biomedical engineering postdoctoral research associate in Janes’ lab. “This map not only reveals the heart's defense mechanisms but also highlights potential weak points that could be reinforced to prevent long-term damage.”

These adaptive responses aren’t just crucial for understanding viral myocarditis — they have the potential to inform treatments for a wide range of viral infections affecting other organs and could also help prevent complications in heart transplant patients by offering new ways to manage immune system interactions.

The findings may also influence the treatment of other chronic conditions linked to viral infections, including cancer therapies.

Publication Information

The study, "Three Modes of Viral Adaption by the Heart," was conducted by researchers Kevin Janes, Cameron Griffiths, Millie Shah, William Shao, and Cheryl A. Borgman from the University of Virginia. It was published in Science Advances, a journal by the American Association for the Advancement of Science (AAAS).

The research was funded by the National Institutes of Health (NIH-NIAID R01-AI186222 and R21-AI105970) and a Packard Fellowship (2009-34710) awarded to Kevin Janes. Additional support came from a Human Frontiers Science Program postdoctoral fellowship (LT000469/2021-L) and a Phil Parrish Postdoctoral Fellowship in Engineering to Cameron Griffiths, as well as an American Heart Association predoctoral fellowship (15PRE24480039) to Millie Shah, the Biotechnology Training Program (T32-GM136615), and the Systems & Biomolecular Data Sciences Training Program (T32-GM145443).

Researchers at the University of Virginia have made a significant discovery that could change how doctors treat viral infections of the heart. The study, published in Science Advances, reveals that the heart responds to viral infections in one of three distinct ways, offering new insights that may lead to better treatments for people at risk of heart failure. These findings bring new hope for patients dealing with viral myocarditis, a condition that can silently damage the heart.

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