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Figure 1. The coxsackievirus B3 life cycle. CAR: Coxsackievirus and adenovirus receptor.
(Figure omitted. See article PDF.)
Figure 2. Signal transduction networks play hub roles to control host-cell responses to coxsackievirus B3 infection. Host-cell permissiveness can be partly determined by host-cell receptors, which are necessary, but not sufficient for virus endocytosis. When viruses enter host-cell cytoplasm, they begin replication. CVB3 has sufficient virulence factors, including viral proteases, host protein shut-off and cleavage of dystrophin to directly drive disease in host cells. However, this step is followed by host cell inflammatory responses, by producing several pro-inflammatory cytokines. Inflammatory responses and disease can persistently support each other to further the progression of disease by developing host cell death, apoptosis or necrosis. We and others have shown that the modified signal pathways within signal-transduction network can be influenced or caused by viral endocytosis, replication and host inflammatory responses. CAR: Coxsackievirus and adenovirus receptor.
(Figure omitted. See article PDF.)
Coxsackievirus of group B3 (CVB3), a cardiotropic virus, is among numerous known etiologies for myocarditis [1,2]. This serotype of enterovirus has been long identified as one of the leading causes of viral myocarditis, a condition that may proceed to acute as well as chronic heart failure. The term myocarditis was coined by Sobernheim in 1837 to refer to inflammation of the myocardium [3]. In fact, CVB3-induced acute myocarditis is almost certainly the early effect of direct virus-induced myocyte damage, followed by host immune and inflammatory responses whose tempo and intensity in part relates to persistent or chronic CVB3 infection. Herein, we review the scientific literature with the particular emphasis on how different CVB3-adapted host cell compartments - including kinases (either at molecular or systems level), host cell-killing, and -eating machineries, matrix metalloproteinases (MMPs), or miRNAs - can underpin virus replication, further the processes of direct CVB3-mediated cardiomyocyte injury and promote the maladaptive inflammatory responses.
Brief history of coxsackieviruses
Enterovirus infections are historically ancient diseases, the earliest and most fully characterized being poliovirus. However, in 1947, certain patients in a milieu of a polio epidemic in the Hudson river town of Coxsackie, NY, USA turned out to have a different virus; this atypical outbreak of poliomyelitis-like illness was reported by Gilbert Dalldorf and Grace Sickles who isolated viruses from fecal...