Grant: Operating Grant

Heart disease is the leading cause of death worldwide. Viral myocarditis (heart muscle cell damage by infection) is an infectious heart disease. Coxsackie virus, a virus discovered in Coxsackie Village near New York City, is a very common causal agent of myocarditis, particularly in children, adolescents and pregnant women. In the late phase of this disease, it often leads to heart failure and death. To date, there is no effective treatment and vaccine. To improve the therapy, it is essential to understand the roadmap of virus-host interactions in the causing of heart disease and find the strategy to design drugs to block the road leading to viral injury of the heart. Heat shock protein 70 (Hsp70) is a key gene involved in response to various biological stresses caused by heat, high pressures, toxic compounds, viral infection, etc. We and others have found that Coxsackievirus infection induces dramatically increase in Hsp70 protein production in the heart. We hypothesize that Coxsackievirus-induced over-production of Hsp70 protein in the heart is responsible for this heart disease. In this project we will study why this virus can increase Hsp70 protein production in the heart, how produced Hsp70 protein can assist virus to cause heart damage and which gene(s) in the roadmap can serve as the potential target for drug development to block the disease occurrence. We will conduct the study first by using isolated heart muscle cells growing in culture dishes and then using the whole heart of mice to mimic human disease. By using mice lacking of Hsp70 gene and comparing with mice having this Hsp70 gene, we will provide better understanding of the roles of Hsp70 in Coxsackievirus-caused heart disease and possibly identify the novel targets in the roadmap for the drug development to treat the viral infection.