Coxsackievirus-induced cardiomyopathy

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Coxsackievirus-induced cardiomyopathy
Specialty Cardiology

Coxsackieviruses-induced cardiomyopathy are positive-stranded RNA viruses in picornavirus family and the genus enterovirus, acute enterovirus infections such as Coxsackievirus B3 have been identified as the cause of virally induced acute myocarditis, resulting in dilated cardiomyopathy. [1] Dilated cardiomyopathy in humans can be caused by multiple factors including hereditary defects in the cytoskeletal protein dystrophin 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. [2]

Contents

Cause

Coxsackievirus shows a cardiac tropism partly due to the high expression of coxsackievirus and adenovirus receptors (CAR) in cardiomyocytes. [3] Coxsackievirus B genome is approximately 7.4 Kb and translated as a polycistronic polyprotein. Upon translation, the polyprotein 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 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. [4]

Viral-induced dilated cardiomyopathy can be characterized using different methods. A 2011 study showed in coxsackievirus infected heart proteome, increased levels of fibrotic extracellular matrix proteins and reduced amounts of energy-producing enzymes can be observed suggesting they could be characteristic in enteroviral cardiomyopathy. [5]

There are notable differences between the hereditary dilated cardiomyopathy in DMD and acute coxsackieviral-mediated cardiomyopathy. [6]

  1. 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.
  2. 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. [7] 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. [8]

Treatment

A wide variety of treatment modalities are currently recommended including Immunosuppressive agents, intravenous immunoglobulins (IVIG), and antiviral agents although the effectiveness of these treatments are not well established and no specific treatment is available. [9]

Related Research Articles

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Coxsackie A virus (CAV) is a cytolytic Coxsackievirus of the Picornaviridae family, an enterovirus.

<span class="mw-page-title-main">Cardiomyopathy</span> Disease of the heart muscle

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<span class="mw-page-title-main">Coxsackie B virus</span> Virus that causes fever and sometimes heart damage

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<span class="mw-page-title-main">Cardiac muscle</span> Muscular tissue of heart in vertebrates

Cardiac muscle is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of the heart. The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall and the inner layer, with blood supplied via the coronary circulation. It is composed of individual cardiac muscle cells joined by intercalated discs, and encased by collagen fibers and other substances that form the extracellular matrix.

<span class="mw-page-title-main">Myocarditis</span> Inflammation of the heart muscle

Myocarditis is inflammation of the cardiac muscle. Myocarditis can progress to inflammatory cardiomyopathy when there is associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The duration of problems can vary from hours to months. Complications may include heart failure due to dilated cardiomyopathy or cardiac arrest.

<span class="mw-page-title-main">Dilated cardiomyopathy</span> Condition involving an enlarged, ineffective heart

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. Complications can include heart failure, heart valve disease, or an irregular heartbeat.

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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.

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References

  1. ↑ Badorff, C; Lee, G. H.; Knowlton, K. U. (2000). "Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex". Herz. 25 (3): 227–32. doi:10.1007/s000590050011. PMID   10904843. S2CID   25973717.
  2. ↑ Badorff, C; Lee, G. H.; Lamphear, B. J.; Martone, M. E.; Campbell, K. P.; Rhoads, R. E.; Knowlton, K. U. (1999). "Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy". Nature Medicine. 5 (3): 320–6. doi:10.1038/6543. PMID   10086389. S2CID   9309488.
  3. ↑ Knowlton, KU (2008). "CVB infection and mechanisms of viral cardiomyopathy". Curr Top Microbiol Immunol. Current Topics in Microbiology and Immunology. 323: 315–35. doi:10.1007/978-3-540-75546-3_15. ISBN   978-3-540-75545-6. PMID   18357777.
  4. ↑ Xiong, D; Lee, G.-H.; Badorff, C.; Dorner, A.; Lee, S.; Wolf, P.; Knowlton, K. U. (2002). "Dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy: a genetic predisposition to viral heart disease". Nature Medicine. 8 (8): 872–7. doi:10.1038/nm737. PMID   12118246. S2CID   5832584.
  5. ↑ Nishtala, K; Phong, T. Q.; Steil, L.; Sauter, M.; Salazar, M. G.; Kandolf, R.; Kroemer, H. K.; Felix, S. B.; Völker, U.; Klingel, K.; Hammer, E. (2011). "Virus-induced dilated cardiomyopathy is characterized by increased levels of fibrotic extracellular matrix proteins and reduced amounts of energy-producing enzymes". Proteomics. 11 (22): 4310–4320. doi:10.1002/pmic.201100229. PMID   21954127. S2CID   5339376.
  6. ↑ Badorff, C; Lee, G. H.; Knowlton, K. U. (2000). "Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex". Herz. 25 (3): 227–32. doi:10.1007/s000590050011. PMID   10904843. S2CID   25973717.
  7. ↑ Sattar, Husain A. (2011). Fundamentals of Pathology: Medical Course and Step 1 Review, First Edition (1st ed.). Chicago, IL: Pathoma. p. 83. ISBN   978-0-9832246-0-0.{{cite book}}: CS1 maint: date and year (link)
  8. ↑ Ammirati, Enrico; Cipriani, Manlio; Moro, Claudio; Raineri, Claudia; Pini, Daniela; Sormani, Paola; Mantovani, Riccardo; Varrenti, Marisa; Pedrotti, Patrizia; Conca, Cristina; Mafrici, Antonio; Grosu, Aurelia; Briguglia, Daniele; Guglielmetto, Silvia; Perego, Giovanni B. (2018-09-11). "Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry". Circulation. 138 (11): 1088–1099. doi:10.1161/CIRCULATIONAHA.118.035319. ISSN   0009-7322.
  9. ↑ Brunetti, L; Desantis, E. R. H (2008). "Treatment of viral myocarditis caused by coxsackievirus B". American Journal of Health-System Pharmacy. 65 (2): 132–137. doi:10.2146/ajhp060586. PMID   18192257.
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