Immunopathological Basis of Virus‐induced Myocarditis

Abstract

Heart diseases are an important cause of morbidity and mortality in industrialized countries. Dilated cardiomyopathy (DCM), one of the most common heart diseases, may be the consequence of infectionassociated myocardits. Coxsackievirus B3 (CVB3) can be frequently detected in the inflamed heart muscle. CVB3-induced acute myocarditis is most likely the consequence of direct virus-induced myocyte damage, whereas chronic CVB3 infection-associated heart disease is dominated by its immunopathological sequelae. Bona fide autoimmunity, for example, directed against cardiac myosin, may favor chronic destructive immune damage in the heart muscle and thereby promote the development of DCM. The immunopathogenesis of myocarditis and subsequent DCM induced either by pathogens or autoantigens can be investigated in well-established animal models. In this article, we review recent studies on the role of viruses, with particular emphasis on CVB3, and different immunological effector mechanisms in initiation and progression of myocarditis.

Wnt11 gene therapy with adeno-associated virus 9 improves the survival of mice with myocarditis induced by coxsackievirus B3 through the suppression of the inflammatory reaction

“…During the same phase, the expression of various cytokines, such as IL-1β, IL-6, TNF-α, IFN-γ, and IP10, can be upregulated in the heart [31,32]. These cytokines play a crucial role in the defense against virus infection [33,34], however, overly robust expression of these cytokines can cause severe inflammation and widespread necrosis of the myocardium [35].…”

Upregulated microRNA-214 enhances cardiac injury by targeting ITCH during coxsackievirus infection

“…Myocarditis most frequently occurs as a result of infection by enteroviruses, and CVB3 is hypothesized to be the most common causative factor in human myocarditis (6). Despite decades of extensive research, the pathogenesis of VM has remained elusive, and there is currently no effective therapy available for the treatment of this disease (20).…”

“…Although VM is frequently resolved among older individuals, it may develop into chronic myocarditis and/or dilated cardiomyopathy, leading to cardiac failure (3)(4)(5). The pathogenesis of VM is based on adverse immune responses evoked by infection of the cardiac muscle with cardiotropic viruses, which leads to viral elimination as well as cardiac myocyte destruction, reparative fibrosis and heart failure (6). Due to the current dearth of effective therapies for the treatment of myocarditis, further studies of the molecular mechanisms underlying these autodestructive inflammatory signaling pathways within the immune system are required (7).…”

Spontaneous autoimmune myocarditis and cardiomyopathy in HLA-DQ8.NODAbo transgenic mice

“…Among viruses, piconavirus coxsackie B3 (CVB3) is most commonly associated with myocarditis. It has been detected in heart of 40–50% of patients with dilated cardiomyopathy(6). Patients with myocarditis have been shown to have marked activation of TNF-α, IL-1 and IL-6(7).…”