Viral myocarditis: receptors that bridge the cardiovascular with the immune system?

Viral myocarditis exhibits different clinical phenotypes depending on the age of the patient. In pediatric patients, viral myocarditis can present as acute heart failure and cardiogenic shock, and in older patients, it often presents as chronic, slowly progressive heart failure and dilated cardiomyopathy. The severity of viral myocarditis is determined by a delicate balance between the viral infection and the inflammatory response that is engendered in the host. The commonest viral causes of human myocarditis include coxsackievirus B group and adenovirus. It is no accident that these two viruses emerged as the commonest etiological agent of myocarditis. Recent elegant work by Bergelson et al1 demonstrated that both of these viruses share a common cell surface receptor—coxsackie-adenoviral receptor (CAR). CAR is a 46-kDa member of the immunoglobulin (Ig) superfamily, featuring the Ig loops maintained by disulphide bonds between appropriately positioned cysteines. The extracellular domain is the key functional component for coxsackievirus internalization.2 CAR also serves as an attachment receptor for adenovirus. However, the natural function and regulation of CAR are still relatively unknown. The efficiency in targeting the host cell by coxsackievirus and adenovirus depends on their distinct coreceptors. Coxsackievirus B (CVB) uses the complement deflecting protein decay accelerating factor (DAF, CD55) as its coreceptor,3 whereas adenovirus uses integrin avb3 and avb5 as its coreceptors.4 DAF as a coreceptor serves an important function by significantly increasing the binding efficiency of coxsackievirus onto the DAF-CAR receptor complex to facilitate internalization by CAR.5