Coxsackievirus Coxsackieviruses are a few related enteroviruses that belong to the ''Picornaviridae'' family of viral envelope, nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus ''Enterovirus'', which also includes poliovi ...

es-induced cardiomyopathy are positive-stranded RNA viruses in

picornavirus Picornaviruses are a group of related Viral envelope, nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, Positive-sense single-stranded RNA virus, positi ...

family and the genus

enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic ...

, acute enterovirus infections such as Coxsackievirus B3 have been identified as the cause of virally induced

acute myocarditis Acute may refer to: Language * Acute accent, a diacritic used in many modern written languages * Acute (phonetic), a perceptual classification Science and mathematics * Acute angle ** Acute triangle ** Acute, a leaf shape in the glossary of leaf m ...

, resulting in

dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. C ...

. Dilated cardiomyopathy in humans can be caused by multiple factors including hereditary defects in the cytoskeletal protein

dystrophin Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costa ...

in Duchenne muscular dystrophy (DMD) patients). A heart that undergoes dilated cardiomyopathy shows unique enlargement of ventricles, and thinning of the ventricular wall that may lead to heart failure. In addition to the genetic defects in dystrophin or other cytoskeletal proteins, a subset of dilated cardiomyopathy is linked to enteroviral infection in the heart, especially coxsackievirus B. Enterovirus infections are responsible for about 30% of the cases of acquired dilated cardiomyopathy in humans. __TOC__

Cause

Coxsackievirus shows a cardiac tropism partly due to the high expression of coxsackievirus and adenovirus receptors (CAR) in cardiomyocytes. Coxsackievirus B genome is approximately 7.4 Kb and translated as a

polycistronic A cistron is a region of DNA that is conceptually equivalent to some definitions of a gene, such that the terms are synonymous from certain viewpoints, especially with regard to the molecular gene as contrasted with the Mendelian gene. The quest ...

polyprotein. Upon translation, the

polyprotein Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...

is cleaved by two essential viral proteases, 2A and 3C. The viral protease 2A cleaves the proteins in a sequence specific manner. These viral proteases can also act on host proteins exerting negative effects on the residing cell. Enteroviral protease 2A can cleave the cytoskeletal dystrophin protein in cardiomyocytes disrupting the dystrophin glycoprotein (DCG) complex. The cleavage site of dystrophin by protease 2A occurs in the hinge 3 region of the protein resulting a disruption of DCG complex and loss of

sarcolemma The sarcolemma (''sarco'' (from ''sarx'') from Greek; flesh, and ''lemma'' from Greek; sheath), also called the myolemma, is the cell membrane surrounding a skeletal muscle fibre or a cardiomyocyte. It consists of a lipid bilayer and a thin ...

integrity and increasing myocyte permeability. This eventually results in similar cardiac deformities observed in dilated cardiomyopathy caused by hereditary defects in dystrophin in DMD patients. Additionally, dystrophin deficiency has been shown to increase the severity in dilated cardiomyopathy in a mouse model for DMD. The increased susceptibility of dystrophin deficient heart to coxsackievirus-induced dilated cardiomyopathy is attributed to more efficient release of the virus from infected cells resulting an increase in viral-mediated cytopathic effects. Viral-induced dilated cardiomyopathy can be characterized using different methods. A 2011 study showed in coxsackievirus infected heart

proteome A proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. P ...

, increased levels of fibrotic

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

proteins and reduced amounts of energy-producing enzymes can be observed suggesting they could be characteristic in enteroviral cardiomyopathy. There are notable differences between the hereditary dilated cardiomyopathy in DMD and acute coxsackieviral-mediated cardiomyopathy. # The amount of virally infected cardiomyocytes varies in different stages of the disease. In a mouse model, at the acute stage (7 days after infection with coxsackievirus B3) approximately 10% of the myocytes are infected and could affect overall cardiac function. In chronic murine infection, the percentage of infected cardiomyocytes are much lower. # Unlike in the DMD, in coxsackievirus induced cardiomyopathy, acute cleavage of dystrophin in cardiomyocytes is unlikely to induce any prompt compensatory mechanism since host cell translation mechanism is defective in the infected cells.

Signs and Symptoms

Coxsackie-induced cardiomyopathy is a potential result of virally induced myocarditis. This cardiomyopathy may present with symptoms such as chest pain, fatigue, heart failure, cardiogenic shock, arrhythmias or sudden death. These symptoms are a by-product of sustained cardiac muscle damage. If Coxsackie-induced cardiomyopathy worsens to heart failure, this may result in systolic dysfunction, with further complications including mitral and tricuspid valve regurgitation and arrhythmias.

Treatment

A wide variety of treatment modalities are currently recommended including

Immunosuppressive agents Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

, intravenous immunoglobulins (IVIG), and antiviral agents although the effectiveness of these treatments are not well established and no specific treatment is available.

References

{{reflist, 30em Heart diseases Enterovirus-associated diseases