Abstract
Globally, coxsackievirus B4 (CV-B4) has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditis and severe central nervous system (CNS) complications, which remain poorly studied and understood. In the present study, we established an Institute for Cancer Research (ICR) mouse model of CV-B4 infection and examined whether CV-B4 infection resulted in a predisposition to myocarditis and CNS infection. We found high survival in both the treatment and control group, with no significant differences in clinical outcomes observed. However, pathological lesions were evident in both brain and heart tissue of the CV-B4-infected mice. In addition, high viral loads were found in the neural and cardiac tissues as early as 2 days post infection. Expressions of IFN-γ and IL-6 in sera were significantly higher in CV-B4-infected mice compared to uninfected negative controls, suggesting the involvement of these cytokines in the development of histopathological lesions. Our murine model successfully reproduced the acute myocarditis and cerebral cortical neuron edema induced by CV-B4, and may be useful for the evaluation of vaccine candidates and potential antivirals against CV-B4 infection.
Highlights
Coxsackievirus B (CV-B) comprises a number of established cardiomyopathy-associated viral serotypes, taxonomically classified within the genus Enterovirus species B, family Picornaviridae
We investigated whether coxsackievirus B4 (CV-B4) infection results in a predisposition to myocarditis and central nervous system (CNS) infection in Institute for Cancer Research (ICR) neonatal mice
Results showed evident pathological lesions in the brain (Figure 2A–D) and heart (Figure 2E–H) tissues in mice infected with CV-B4 LY114F, including cerebral cortical neuron edema (Figure 2B) and myocardial lymphocytic infiltration (Figure 2F)
Summary
Coxsackievirus B (CV-B) comprises a number of established cardiomyopathy-associated viral serotypes, taxonomically classified within the genus Enterovirus species B, family Picornaviridae. There are currently 63 recognized enterovirus serotypes (www.picornaviridae.com) with diverse tissue tropisms and correspondingly broad spectrum of disease presentation, including myocarditis, encephalitis, paralysis, meningitis, upper and lower respiratory disease, pleurodynia, herpangina, myopericarditis, pancreatitis, and type I diabetes (Knowles et al, 2011; Tapparel et al, 2013). In the prior two decades, 1the relationship between CV-B and myocarditis/dilated cardiomyopathy has been substantiated. CV-B infections have been identified in approximately 25%–40% cases of acute myocarditis and dilated cardiomyopathy in young adolescents and adults (Gaaloul et al, 2014; Leonard, 2004). CV-B4 is associated with severe central nervous system (CNS) complications and neurological sequelae (Zhu et al, 2015)
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