Coxsackievirus-induced chronic myocarditis in murine models

Area of Science:

• Virology
• Immunology
• Cardiology

Background:

• Coxsackievirus B3 (CVB3) infection is a leading cause of viral myocarditis.
• Chronic myocarditis can develop following acute CVB3 infection, with unclear underlying mechanisms.
• Autoimmune responses, particularly molecular mimicry, are hypothesized to contribute to chronic inflammation.

Purpose of the Study:

• To investigate the role of autoimmune responses in CVB3-induced chronic myocarditis.
• To explore the hypothesis of molecular mimicry between CVB3 antigens and cardiac myosin.
• To determine if pre-existing antibodies to cardiac myosin can influence CVB3 myocarditis severity.

Main Methods:

• Infection of multiple murine strains with virulent CVB3 variants.
• In situ hybridization to detect viral RNA in heart tissue at various time points post-inoculation.
• Challenge studies with CVB3 and/or human cardiac myosin (HM) or its synthetic peptides.
• Antibody analysis against CVB3 and cardiac myosin.

Main Results:

• Viral genomic RNA was detected early post-inoculation but rarely during chronic inflammation, suggesting limited viral replication.
• Mice pre-inoculated with HM showed reduced myocarditis severity after CVB3 challenge, indicating a protective role.
• HM inoculation alone induced non-neutralizing antibodies against CVB3 and, in some cases, cardiomyopathy.
• Peptide immunization studies demonstrated cross-reactivity between anti-CVB3 and anti-cardiac antibodies.

Conclusions:

• Autoimmune responses, driven by molecular mimicry between CVB3 and cardiac myosin, likely play a significant role in chronic myocarditis.
• Antibodies to cardiac myosin may offer protection by binding and reducing viral burden.
• Conversely, autoimmune reactions can also exacerbate heart disease, highlighting a complex interplay.