Grant: CIHR Fellowship

This project studies a virus, called coxsackievirus B3 (CVB3), that infects the heart. CVB3 is a very common virus; most infected people have mild symptoms and recover completely. Sometimes, the infection is not removed by the immune system and the virus remains in the heart for months to years. This long-term infection steadily damages the heart, leading to a condition called dilated cardiomyopathy. The only treatment for dilated cardiomyopathy is heart transplant. As a result, dilated cardiomyopathy is one of the main reasons for heart transplantation, especially in people under 40 years of age. It is not well known why some CVB3 infections resolve, while others shift to a long-term state. A heart infection disrupts cells in the heart. The heart cells then adapt to this disruption in different ways. Upon starting my project, I found three different ways that heart cells can adapt to long-term infection. I propose that whether or not an infection becomes long-term depends on which way the heart cells adapt. I will test this idea by interfering with how cells can adapt. I will also use computer-based techniques to simulate the short-term and long-term infections in search of additional clues. Finally, I will look at heart cell adaptations in humans by using data obtained from patients with dilated cardiomyopathy. Most research on CVB3 has tried to reduce the complexity of infection down to a few key components. This approach was successful for describing long-term infections in other viruses, such as the human immunodeficiency virus (HIV), but it has not worked for CVB3. Instead of breaking down viral complexity, my proposal takes advantage of it by using large-scale measurements and computer-based techniques. By improving our understanding of why some CVB3 infections progress to the long-term state, this work could open up new options to prevent dilated cardiomyopathy. The project also sets an example for studying other viral infections from a new perspective.