The tyrosine kinase p56(lck) is essential in coxsackievirus B3-mediated heart disease

Infections are thought to be important in the pathogenesis of many heart di seases. Coxsackievirus B3 (CVB3) has been linked to chronic dilated cardiom yopathy, a common cause of progressive heart disease, heart failure and sud den death. We show here that the sarcoma (Src) family kinase Lck (p56(kk)) is required for efficient CVB3 replication in T-cell lines and for viral re plication and persistence in vivo. Whereas infection of wild-type mice with human pathogenic CVB3 caused acute and very severe myocarditis, meningitis , hepatitis, pancreatitis and dilated cardiomyopathy, mice lacking the p56( lck) gene were completely protected from CVB3-induced acute pathogenicity a nd chronic heart disease. These data identify a previously unknown function of Src family kinases and indicate that p56(lck) is the essential host fac tor that controls the replication and pathogenicity of CVB3.