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Coxsackievirus B3-induced myocarditis: differences in the immune response of C57BL/6 and Balb/c mice
Carola Leipner1, Katja Grün, Ilka Schneider
1Institute of Virology and Antiviral Therapy, Medical Centre at the Friedrich Schiller University Jena, Hans-Knöll-Strasse 8, 07745 Jena, Germany. carola.leipner@uni-jena.de
Insights
Coxsackievirus B3 (CVB3) infection can cause myocarditis. This study found that a strong virus-specific IgG antibody response is crucial for effectively eliminating CVB3 from infected hearts in mice.
Area of Science:
- Virology
- Immunology
- Cardiovascular Science
Background:
- Coxsackievirus B3 (CVB3) is a primary cause of human myocarditis, potentially leading to dilated cardiomyopathy (DCM).
- Viral persistence in the heart can activate fibroblasts, causing myocardial fibrosis and impaired function.
- Immune system defects can hinder viral clearance, promoting persistence.
Purpose of the Study:
- To investigate the immune response differences between two immunocompetent mouse strains (C57BL/6 and Balb/c) following CVB3 infection.
- To determine the role of specific immune responses in viral clearance from the heart.
Main Methods:
- Infection of C57BL/6 and Balb/c mice with CVB3.
- Monitoring viral load in heart tissue.
- Quantifying cytokine mRNA levels in the heart.
- Assessing virus-specific IgG and IgM antibody responses.
Main Results:
- Both mouse strains recovered from CVB3 infection with similar cardiac cytokine mRNA levels.
- Viral clearance from heart tissue was slower in Balb/c mice compared to C57BL/6 mice.
- C57BL/6 mice exhibited a strong virus-specific IgG response and a weak IgM response, unlike Balb/c mice.
Conclusions:
- Virus-specific IgG antibodies play a significant role in the elimination of Coxsackievirus B3 from infected cardiac tissue.
- Immune response kinetics, particularly IgG production, influences viral clearance rates in myocarditis.
Abstract:
Coxsackievirus B3 (CVB3) infections are the most frequent causes of human myocarditis, often resulting in chronic stages characterized by fibrosis and loss of function. This disease is called dilated cardiomyopathy (DCM). Persistent virus in the myocardium may lead to chronic activation of fibroblasts, and subsequently, to fibrosis of the myocardium. Studies with immunodeficient mice have shown that certain defects of the immune system retard the rate at which virus is eliminated from the heart, thus leading to viral persistence. Therefore, we followed the immune response of two immunocompetent mouse strains (C57BL/6 and Balb/c) to CVB3 infection. These two strains have been reported to develop different immune responses to infections and we expected a similar reaction to viral infections as well. The two mouse strains recovered completely from CVB3 infection and expressed identical levels of cytokine mRNA in the heart. However, the virus in heart tissue decreased more slowly in Balb/c than in C57BL/6 mice. This was accompanied by a strong virus-specific IgG and weak IgM response in the C57BL/6 mice, in comparison to the Balb/c mice. We conclude, therefore, that viral-specific IgG is of importance for CVB3 elimination from infected hearts.