MDA5

Abstract

Myocarditis is an inflammation of the heart muscle, which frequently follows microbial infections. Picornaviruses and adenoviruses are the most commonly identified viral etiologic agents.1 Cardiac injury results from both virus infection/replication and host inflammatory responses, but in either case, elimination of the virus from the heart can have a beneficial effect on disease outcome as is evident from clinical trials treating biopsy-proven, virus-positive patients with interferon β (IFNβ).2 The success of type I IFN therapy in myocarditis may partly depend on the initiating etiologic agent, as virus clearance and cardiac improvement was greater in patients with enteroviruses than with parvovirus B19 or human herpesvirus 6.2 This finding is not surprising as it is well known that virus families vary dramatically in their sensitivity to type I IFN, in part because many viruses have developed immune evasion mechanisms targeting this innate host defense mechanism.3 Enteroviruses of the Picornavirus family are small, nonenveloped, positive-sensed, single-stranded RNA viruses, which are classically among the most sensitive to type I IFN, with encephalomyocarditis virus (EMCV) being one of the most IFN sensitive of the enteroviruses.4 Article see p 326 Type I IFN are induced through virus-sensing pattern recognition receptors (PRR) of the innate immunity system, which recognize shared pathogen-associated molecular patterns between many infectious agents.5 PRRs include Toll-like, retinoic acid-inducible gene I (RIG-I)-like, nucleotide-binding oligomerization domain receptors (NOD)-like, C-type lectin and possibly absent in melanoma 2 (AIM2)-like receptors; a diverse subcellular compartmentalization of the pattern recognition receptors allows optimal recognition of their relevant pathogen-associated molecular patterns. Toll-like receptors (TLR) are primarily implicated in reacting to extracellular bacterial pathogen-derived molecules (TLR5 [flagellin], TLR4 [lipopolysaccharide], TLR2/1, or TLR2/6 [lipoprotein]) and are located in the plasma membrane; in contrast, RIG-I-like (single-stranded/double-stranded RNA) and NOD-like (muramyl tripeptide/muramyl dipeptide) receptors are located in the …