Grant: Operating Grant

Virus infection of the heart, termed viral myocarditis, can result in subsequent heart failure, and is one of the most prevalent causes of disease and death worldwide. Coxsackievirus is one of the primary causes of viral myocarditis, particularly in children. There is currently no effective pharmaceutical treatment available for viral myocarditis. Autophagy is a cellular "selfeating" process by which cells dispose of damaged organelles and unwanted proteins. Autophagy affects many fundamental cellular functions including cell division, quality control of newly produced proteins, and immune defense. Impairment of this system has been linked to several human diseases, including cancer, neurodegenerative, ageing, and cardiovascular diseases. We have recently demonstrated a critical role of autophagy in the regulation of coxsackieviral replication. In this project, we propose to utilize a multidisciplinary approach of cell biological, molecular biological, and genetic procedures to elucidate the detailed mechanisms by which coxsackievirus utilizes or subverts the host autophagy machinery to achieve successful replication. We also propose to investigate the functional role of the autophagy in viral myocarditis and to evaluate autophagy as drug target for therapeutic purpose. These studies will provide valuable insights into the cellular and molecular mechanisms of viral myocarditis and will assist in development of new therapeutic approaches to limit viral replication and to reduce virus-induced damage of the heart.