Project 172008

Myocarditis is a condition that results in inflammation of heart muscle. It has been suggested that myocarditis and dilated cardiomyopathy (DCM) are successive stages of a progressive autoimmune disease of the heart. This condition can progress to a stage that requires a heart transplantation or sudden death in young adults. Myocarditis is often brought on by a viral infection. In humans, coxsackie B viruses (CBV) are the most frequent cause of viral induced myocarditis. It is estimated that 30% of new DCM cases in North America are the result of coxsackievirus infection. After viral infection, disease resistant individuals develop a short-lived disease while in other disease susceptible individuals the disease progresses to a chronic, autoimmune disease. The objective of our project is to determine how disease progresses from the short-lived disease to the chronic disease. As mice develop a similar disease to humans after CBV infection, we will be using disease resistant and disease susceptible mice to determine which cellular components are involved in causing long-term myocarditis. Using a variety of mice that are missing a single component of their immune system, we can determine which immune components are important in disease initiation. We will infect these mice with CBV and monitor them for development of chronic myocarditis. If a mouse deficient of a certain component of their immune system doesn't develop the chronic disease after CBV infection, we will know that this component is likely involved in the progression from a short lived disease into a chronic disease. Alternatively, we will treat the mice with environmental agents that stimulate the immune system at the same time as CBV infection. If adding these agents causes an increase in chronic disease, we will have identified important information with regard to how disease advances. In turn, these findings would translate into novel therapeutic approaches towards disease prevention.