Grant: Operating Grant

Worldwide, heart disease is the leading cause of death, particularly in developed countries. Virally caused heart disease called myocarditis (heart muscle cell injury) is one of the common heart diseases, particularly in children, young adults and pregnant women. Coxsackie virus, a virus that was discovered in a small town called Coxsackie near New York City, is ranked the #1 virus that can cause this heart disease. This virus can infect multiple organs of humans, but the degrees of infection are different. For example, heart and pancreas can be easily infected by this virus and develop deadly diseases shortly after infection, particularly in the heart. However kidney and lung are hardly infected by this virus and thus no disease is developed. This phenomenon can not be explained very well with the current knowledge. Therefore, the goal of this grant is to search for the genes or molecules in the body that determine why Coxsackie virus can easily infect the heart but not the kidney. Recently, a group of small genetic molecules called microRNAs (miRNA) has been found to play an important role in controlling virus infection in other diseases. Based on this finding, we hypothesize that this newly discovered group of miRNAs may control the degree of easiness of infection in different organs, such as the heart and kidney. To test this hypothesis, we will first search for and evaluate the miRNA production in different cell cultures or in different organs of mice. Then we will select several important miRNAs that either produce a lot or produce a little and test their functions in controlling viral infection and growth in the heart muscle cells using culture dishes. At the same time, we will use kidney cells to perform the same experiment for comparisons. Finally, these experiments will be verified by using mice, an established animal model mimicking human heart disease. These experiments are aimed to find a strategy to block virus infection.