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Extracellular matrix remodelling after coxsackievirus B3-induced murine myocarditis
R M Gómez1, C G Castagnino, M I Berría
1Department of Microbiology, Faculty of Medicine, University of Buenos Aires, Argentina.
Abstract:
Weanling inbred Balb/c mice were intraperitoneally inoculated with a myocarditic variant of coxsackievirus B3. At days 1, 2, 4, 6, 8, 10, 14, 24 and 30 post-infection (p.i.), myocardial tissue was harvested for viral infectivity titrations and histological studies, including routine techniques (haematoxylin-eosin, Masson trichrome and von Kossa) and specialized procedures (silver impregnation for reticulin, picrosirius red stain for collagen and immunoperoxidase labelling for laminin). Virus was isolated as from day 2, reached maximal infectivity at days 6-8 and decreased gradually to become undetectable by day 14. Early histological findings during the 1st week consisted mainly of scattered foci of necrotic myocytes showing calcium deposits; slight mononuclear cell infiltration and fragmentation of both reticulin fibres and pericellular laminin were also present. From the 2nd up to 4th week p.i., inflammatory reaction abated concomitantly with the gradual development of fibrosis, as evidenced by reticulin fibre thickening, irregular laminin distribution and collagen fibre increase. Our results suggest that viral-induced necrosis is able to trigger marked extracellular matrix remodelling even in the case of minimal inflammation.
Insights
Coxsackievirus B3 infection in mice causes heart cell death and calcium deposits early on. Later, minimal inflammation leads to significant scar tissue formation and extracellular matrix remodeling in the heart.
Area of Science:
- Virology
- Pathology
- Cardiology
Background:
- Coxsackievirus B3 (CVB3) is a common cause of viral myocarditis.
- Understanding the host response to CVB3 infection is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the temporal relationship between viral replication, myocyte necrosis, inflammation, and extracellular matrix remodeling in CVB3-induced myocarditis.
- To elucidate the role of viral-induced necrosis in triggering cardiac fibrosis.
Main Methods:
- Weanling Balb/c mice were infected with a myocarditic CVB3 variant.
- Myocardial tissue was collected at multiple time points post-infection.
- Viral infectivity titrations and histological analyses (H&E, Masson trichrome, von Kossa, silver impregnation, picrosirius red, immunoperoxidase labelling for laminin) were performed.
Main Results:
- Viral replication peaked at days 6-8 post-infection and became undetectable by day 14.
- Early findings included myocyte necrosis with calcium deposits, minimal mononuclear cell infiltration, and fragmentation of reticulin and laminin.
- Later stages showed abated inflammation with progressive fibrosis, characterized by thickened reticulin fibers, altered laminin distribution, and increased collagen.
Conclusions:
- Viral-induced myocyte necrosis can initiate significant extracellular matrix remodeling.
- Cardiac fibrosis develops even with minimal inflammatory response in CVB3 myocarditis.
- These findings highlight the complex interplay between viral infection, cell death, and cardiac tissue repair.