Innate immune mechanisms of viral myocarditis: Role of the cytosolic DNA-sensing pathway

Coxsackie virus B (CVB) is the number one cause of viral heart inflammation leading to heart failure and sudden death in ~20 percent of infected children and young adults. In most people, CVB infection causes mild symptoms. However, individuals with underdeveloped and/or compromised immune systems are at increased risk of severe disease. Normally, our healthy immune system acts as a first line of defense against viruses, but excessive and sustained activation of our immune system can be harmful, leading to chronic inflammation and injuries to the heart. The objective of my project is to study how CVB hijacks a novel immune pathway called cGAS-STING, to trigger harmful inflammation in the heart. Our knowledge gap is that we do not completely understand how CVB hijacks the cGAS-STING immune pathway and whether blocking this pathway with drugs can protect the heart. To accomplish this goal, we will precisely identify which cells and immune pathways are responsible for harmful inflammation of the heart. Findings from this study have the potential to open new therapeutic avenues to combat existing and emerging viral threats.