Coxsackievirus B3 (CVB3) is one of the globally distributed human pathogenic enteroviruses of the family Picornaviridae, which are associated with disease patterns such as aseptic meningitis, pancreatitis, type 1 diabetes (Curr Diab Rep. 2010;10(5):350-6.), but especially myocarditis is associated and can unexpectedly lead to sudden cardiac death, especially in people under 40 years of age (Eur Heart J. 2013;34(33):2636-48.). It has been postulated that at least 35% of the population undergo acute viral myocarditis in the course of life, which in most cases is clinically inapparent. In recent years, the introduction of molecular biology methods into the diagnosis of myocarditis has demonstrated that detection of CVB3 RNA is also successful in a proportion of patients with chronic myocarditis and dilated cardiomyopathy (17%), indicating that a proportion of these diseases develop on the floor of persistent infection (Proc Natl Acad Sci U S A. 1987; 84(17):6272-6.; New Engl J Med 2000, 343:1388-1398.).

For the study of pathogenesis mechanisms of viral myocarditis, it is advantageous that CVB3 can also induce acute and chronic myocarditis in susceptible mouse strains (Proc Natl Acad Sci U S A. 1992; 89(1):314-8), which is often associated with cardiac arrhythmias (FASEB J. 2013; 27(10):4108-21.), in line with findings in humans. The course of CVB3 myocarditis is highly dependent on cellular factors (J Virol. 2014 Jul 1;88(13):7345-56) as well as the effectiveness of the immune response in the early phase of infection, with natural killer cells playing an important role (J Pathol. 2014 May 5. doi: 10.1002/path.4369. [Epub ahead of print]). The dysregulation of cell metabolism seen in chronic myocarditis is associated with heme oxygenase 1 (HO-1)-mediated oxidative stress (Cell Physiol Biochem. 2014;33(1):52-66) and the release of (pro-) inflammatory cytokines and proteins such as connective tissue growth factor, CTGF (J Mol Med (Berl). 2008; 86(1):49-60) and osteopontin (Circ Res. 2009 104(7):851-9.), which are crucial in remodeling processes of the myocardium due to inflammatory responses.

For the detection of CVB3 on human and murine tissues and cells is now available from Mediagnost an antibody is available that is able to recognize the viral envelope protein VP1 in a highly specific and highly sensitive manner, as already shown in the following publications:

Freiberg F, Sauter M, Pinkert S, Govindarajan T, Kaldrack J, Thakkar M, Fechner H, Klingel K, Gotthardt M. Interspecies Differences in Virus Uptake versus Cardiac Function of the Coxsackievirus and Adenovirus Receptor. J Virol.2014 Jul 1;88(13):7345-56.

Klingel K, Fabritius C, Sauter M, Göldner K, Stauch D, Kandolf R, Ettischer N, Gahlen S, Schönberger T, Ebner S, Makrigiannis AP, Bélanger S, Diefenbach A, Polić B, Pratschke J, Kotsch K. The Activating Receptor NKG2D of Natural Killer Cells Promotes Resistance against Enterovirus-Mediated Inflammatory Cardiomyopathy. J Pathol. 2014 May 5. doi: 10.1002/path.4369. [Epub ahead of print]

Ursu ON, Sauter M, Ettischer N, Kandolf R, Klingel K. Heme oxygenase-1 mediates oxidative stress and apoptosis in coxsackievirus b3-induced myocarditis.Cell Physiol Biochem. 2014;33(1):52-66.

Ettischer-Schmid N, Normann A, Sauter M, Kraft L, Kalbacher H, Kandolf R, Flehmig B, Klingel K. A new monoclonal antibody (Cox mAB 31A2) detects VP1 protein of coxsackievirus B3 with high sensitivity and specificity. Virchow's Arch
DOI 10.1007/s00428-016-2008-8