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Coxsackievirus B-3 myocarditis. Identification of different pathogenic mechanisms in DBA/2 and Balb/c mice
Abstract:
DBA/2 and Balb/c mice, both H-2d, develop myocardial inflammation and necrosis when infected with a heart-adapted strain of coxsackievirus Group B, Type 3. Similar inoculation of C57Bl/6 (H-2b) animals results in minimal myocarditis despite equivalent heart virus titers in the three stains. Thus, the host's genetic constitution influences the pathogenesis of the infection. Anti-mouse thymocyte serum and monoclonal Iad antibody effectively prevent myocarditis induction in DBA/2 and Balb/c mice, which demonstrates the importance of the immune system in this disease. Cytolytic T lymphocytes lysing virus-infected and uninfected myocytes and heart-reactive autoantibodies occur in both myocarditis-susceptible strains. Cellular immunity causes the myocardial injury in Balb/c mice. Complement depletion of Balb/c mice using cobra venom factor fails to alter the disease. Similar treatment of DBA/2 animals abrogates inflammation and necrosis, which suggests that heart-reactive antibodies in this strain are primarily responsible for initiating myocardial damage.
Insights
Host genetics influence coxsackievirus myocarditis. Immune responses, specifically cellular immunity in Balb/c and autoantibodies in DBA/2 mice, drive myocardial damage, highlighting distinct immune mechanisms in viral heart disease.
Area of Science:
- Immunology
- Virology
- Cardiovascular Science
Background:
- Coxsackievirus B3 (CVB3) infection can cause myocarditis, inflammation of the heart muscle.
- Genetic background significantly impacts disease severity in viral myocarditis models.
- Previous studies suggest a role for the immune system in CVB3-induced heart disease.
Purpose of the Study:
- To investigate the role of host genetic factors in CVB3 myocarditis pathogenesis.
- To elucidate the specific immune mechanisms responsible for myocardial injury in different mouse strains.
- To determine the contribution of cellular immunity versus autoantibodies in CVB3-induced heart damage.
Main Methods:
- Infection of DBA/2, Balb/c (H-2d), and C57Bl/6 (H-2b) mice with a heart-adapted CVB3 strain.
- Assessment of myocardial inflammation, necrosis, and viral titers.
- Immunomodulation using anti-mouse thymocyte serum, anti-Iad antibody, and complement depletion (cobra venom factor).
- Analysis of cytolytic T lymphocyte activity and heart-reactive autoantibodies.
Main Results:
- DBA/2 and Balb/c mice developed significant myocarditis, while C57Bl/6 mice showed minimal inflammation despite similar viral loads.
- Immune suppression (anti-thymocyte serum, anti-Iad antibody) prevented myocarditis in susceptible strains.
- Balb/c mice primarily exhibited myocardial injury mediated by cellular immunity.
- DBA/2 mice showed abrogation of myocarditis upon complement depletion, indicating a role for heart-reactive antibodies.
Conclusions:
- Host genetic background dictates susceptibility and pathogenesis of CVB3 myocarditis.
- Distinct immune mechanisms, cellular immunity in Balb/c and autoantibodies in DBA/2, drive myocardial damage.
- Targeting specific immune pathways may offer therapeutic strategies for viral myocarditis.