Nasal cardiac myosin peptide treatment and OX40 blockade protect mice from acute and chronic virally-induced myocarditis

Myocarditis poses a severe health problem, can lead to dilated cardiomyopathy (DCM) and death, and is thought to be triggered by infections. Enteroviruses such as Coxsackie virus B 3 (CVB3) have been implicated as a culprit, since they can cause acute and chronic heart disease in susceptible mice. CVB was detected in human cardiac myocytes in some cases, whereas acute CVB infection was thought to have caused death. Here we studied, whether nasal administration of cardiac myosin (CM) major histocompatibility class (MHC) II peptides CM947-960 and CM735-747 and OX40 blockade would be able to ameliorate immunopathology and heart disease in BALB/C mice infected with CVB3. We found that nasal CM-peptide prophylactic treatment significantly reduced myocarditis and mortality by enhancing Treg and IL-10 induction and that blockade of OX40 signaling could reduce heart inflammation when administered late during pathogenesis. Altogether, these results chart the way for novel prevention and intervention strategies for viral myocarditis.