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Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis
K Klingel1, C Hohenadl, A Canu
1Max-Planck-Institut für Biochemie, Martinsried, Federal Republic of Germany.
Abstract:
Coxsackievirus B3-induced myocarditis in different immunocompetent mouse strains was used as a model to investigate interrelationships between virus replication and development of chronic enteroviral heart disease. Using in situ hybridization to detect enteroviral RNA, we show that heart muscle infection is not only detected in acute myocarditis but is also detected during the chronic phase of the disease. Coxsackievirus B3 could evade immunological surveillance in a host-dependent fashion, thus inducing a persistent infection of the myocardium in association with ongoing inflammation. Patterns of acute and persistent myocardial infection were quantitatively assessed in one representative mouse strain (A.CA/SnJ, H-2f) by applying computer-assisted digital image processing; these patterns were then related to the extent of myocardial tissue damage as well as to inflammation. We observed a strong correlation, both spatial and temporal, between viral replication and development of myocardial lesions, indicating that acute and chronic myocardial injuries are a consequence of multifocal organ infection. Analysis of strand-specific in situ hybridization revealed that viral replication in persistent infection is restricted at the level of RNA synthesis. The described procedure for quantitating organ infection provides a powerful tool for evaluating virus-host interactions and will be of particular interest to those studying human enterovirus-induced cardiomyopathies.
Insights
Persistent Coxsackievirus B3 infection in the heart muscle, detected via in situ hybridization, correlates with myocardial damage and inflammation. This viral persistence, a host-dependent evasion of immune surveillance, drives chronic enteroviral heart disease.
Area of Science:
- Virology
- Immunology
- Cardiology
Background:
- Enteroviral infections, particularly Coxsackievirus B3, are a significant cause of myocarditis and chronic heart disease.
- Understanding the interplay between viral replication and host immune response is crucial for managing enteroviral cardiomyopathies.
Purpose of the Study:
- To investigate the relationship between Coxsackievirus B3 replication and the development of chronic enteroviral heart disease using a mouse model.
- To determine if viral presence persists beyond the acute phase of myocarditis and contributes to chronic cardiac pathology.
Main Methods:
- Utilized immunocompetent mouse strains infected with Coxsackievirus B3 to model myocarditis.
- Employed in situ hybridization to detect enteroviral RNA in myocardial tissue.
- Applied computer-assisted digital image processing for quantitative assessment of viral infection patterns and myocardial damage.
Main Results:
- Enteroviral RNA was detected in the heart muscle during both acute and chronic phases of myocarditis.
- Coxsackievirus B3 demonstrated host-dependent evasion of immunological surveillance, leading to persistent myocardial infection and inflammation.
- A strong spatial and temporal correlation was observed between viral replication and the development of myocardial lesions.
- Persistent viral replication was found to be restricted at the RNA synthesis level.
Conclusions:
- Acute and chronic myocardial injuries in enteroviral heart disease result from multifocal organ infection.
- Persistent Coxsackievirus B3 infection, characterized by restricted RNA synthesis, plays a key role in the pathogenesis of chronic enteroviral cardiomyopathies.
- The quantitative methods developed offer a valuable tool for studying virus-host interactions in enteroviral heart disease.