Adenovirus Myocarditis

Jason B. Weinberg, MD

Associate Professor of Pediatrics & Communicable Diseases Associate Professor of Microbiology & Immunology)

Charles Woodson Interdisciplinary Award in Children’s Health ($30,000)

Immunoproteasome Activity in Adenovirus Myocarditis

Myocarditis is an inflammation of the myocardium, the middle layer of the heart wall Acute myocarditis is a significant cause of disease in childhood. Myocarditis has been identified in 16 to 21% of sudden deaths in children. Viruses are major causes of acute myocarditis. Viral myocarditis is often more severe and sudden in onset in newborns and infants than in older patients, with up to 67% mortality in newborns and 55% in infants less than 1 year of age, compared to 20 to 25% in older children and 38% in adults.

Although viral myocarditis is a significant cause of disease, there are currently no therapies that have shown consistent benefit for patients with myocarditis caused by the adenoviruses or by other viruses. Very little is known about susceptibility factors that contribute to the cause of adenovirus myocarditis. We anticipate that the research we are proposing will provide insight into contributions of host proteasome and immunoproteasome activity to control of viral replication and to virus-induced cardiac inflammation. In doing so, we hope to establish these host processes as novel targets for therapy in patients with viral myocarditis. Funding will provide support for these experiments, generating critical preliminary data for larger-scale proposals that will be submitted to the National Institutes of Health (NIH) and the American Heart Association . The majority of the funds will be used for the purchase, housing, and care of animals used in the experiments described in our proposal. Additional funds will be used to purchase other laboratory supplies (for example, antibodies, enzymes for PCR, ELISA reagents, tissue culture supplies necessary for generating viral stocks) required to conduct the experiments.