Nucleic Acid-Based Strategies for the Treatment of Coxsackievirus-Induced Myocarditis

Viral myocarditis is the most common heart disease in infants, children, young adults and pregnant women. Although a number of viruses from different genera, such as adenovirus, hepatitis C virus (HCV), parvoviruses and cytomegalovirus have been reported to cause myocarditis (Bowles et al., 2003; Kindermann et al., 2008; Kuhl et al., 2005a; Kuhl et al., 2005b; Kyto et al., 2005; Mahrholdt et al., 2006; Matsumori, 2005; Matsumori et al., 2006), coxsackievirus, particularly coxsackievirus B3 (CVB3), is generally considered the primary etiological agent of myocarditis (Blauwet, 2010; Kuhl et al., 2005a; Mahrholdt et al., 2006). CVB3 infection of the heart is often persistent and enters the chronic phase, leading to dilated cardiomyopathy (DCM)(Andreoletti et al., 2009; L. T. Cooper, Jr., 2009; Kuhl et al., 2005b; Yajima& Knowlton, 2009), a squelae of viral myocarditis characterized by ventricular chamber dilation, increased wall thickness, weaker beating and abnormal heart function. Patients with DCM eventually develop into congestive heart failure. To date, there is no clinically proven specific treatment available for viral myocarditis and DCM. Patients with DCM eventually need heart transplantation as the final treatment (Schultz et al., 2009). The managements for viral myocarditis are usually supportive therapies, such as improvements in cardiophysiology with medicine used to treat other kinds of heart diseases, and application of non-specific antiviral agents to decrease the viral load. The former measurements include administration of angiotensin-converting enzyme inhibitor or angiotensin receptor blockade, beta-adrenergic blockade, diuretics, etc (Dennert et al., 2008; Rose, 2009; Schultz et al., 2009); the later measurements include application of type I interferons or nucleotide analogs such as ribavirin, which is reviewed elsewhere (Blauwet, 2010; Dennert& Crijns& Heymans, 2008; Schultz et al., 2009). If myocarditis was caused by an autoimmune disorder, it would be appropriately treated by immunosuppression (Rose, 2009; Schultz et al., 2009). However, the effectiveness of treatment with immunosuppressive therapies has not reached a consensus amongst different studies. This can probably be attributed to the difficulty of confirmation and diagnosis of the etiology and pathogenesis of myocarditis. Thus it is very important to distinguish infectious and autoimmune disease since the same methods of treatment will not be optimal for both forms of heart muscle diseases. The diagnostic gold standard is endomyocardial biopsies with the histological Dallas criteria, in association with new