Grant: Project Grant

In North America and globally, heart disease is still the leading cause of death. Viral myocarditis (damage of heart muscle cells by viral infection) is an infectious heart disease. Coxsackie-virus is a very common cause of myocarditis, particularly in children and people < 40 years old. This disease can often lead to heart failure and sudden unexpected death. Currently, there is no effective treatment or vaccine available. To develop a treatment, it is essential to first understand how the virus destroys the heart muscle cells during infection. In our early experiments to identify the genes damaged by viral infection, we found that a gene called NFAT5 may be of importance. The NFAT5 gene is initially known to be protective to our body through study of kidney disease. However, its role in the heart is not known. We found that NFAT5 can protect the heart by enhancing production of protective proteins against coxsackie-virus infection. However, we further found that NFAT5 protein is damaged by viral infection (i.e., the virus cuts the NFAT5 protein into 2 fragments); this damage decreases the ability of heart cells to defend against infection, leading to increased viral growth and heart muscle cell injury. To better understand this mechanism, we will grow mouse heart muscle cells in Petri dishes and replace the full-length NFAT5 gene with NFAT5-fragments in these cells to mimic the viral infection. The anti-viral activities of the cells containing the full-length NFAT5 gene will be compared to those cells that have the NFAT5 fragments. We will also do a similar experiment using genetically modified mice. These studies will help us confirm that virus-caused damage of the NFAT5 gene can increase viral multiplication and lead to heart muscle cell death. Based on these results, we will have a better understanding on why viral infection can cause heart disease and how we can prevent and treat this disease by enhancing NFAT5 protein production in our body.