Beyond the Infection: The Immunopathological Cascade and Novel Therapeutic Avenues in Viral Myocarditis

Figures

• 

  FIGURE 1. Overview of the acute immunopathological cascade and therapeutic avenues in viral myocarditis. Cardiotropic viral invasion directly damages cardiomyocytes and cardiac microvascular endothelial cells, inducing active viral replication and the release of damage‐associated molecular patterns (DAMPs). These danger signals trigger innate immune activation, while virus‐induced intracellular stress drives NLRP3 inflammasome assembly, mediating cell pyroptosis and a localized cytokine storm. Persistent viral antigen exposure, active transcription, and molecular mimicry further activate autoimmune responses driven by autoreactive T cells and cardiac autoantibodies. These combined insults promote chronic smoldering inflammation, extracellular matrix accumulation, and diffuse myocardial fibrosis, ultimately driving the progression toward dilated cardiomyopathy (DCM) and end‐stage heart failure. Created in BioRender (https://www.biorender.com/).

• 

  FIGURE 2. Mechanisms of dysregulated repair and ventricular remodeling during the chronic phase. Persistent viral infection or acute immunoregulatory imbalance acts as the primary driver toward cardiac remodeling. Dysregulated macrophage polarization shifts the balance: Proinflammatory M1 macrophages remain dominant, secreting TNF‐α, IL‐1β, and IL‐6 to perpetuate tissue inflammation and extracellular matrix (ECM) degradation, while dysfunctional M2 macrophages abnormally secrete TGF‐β. Simultaneously, persistent Th1 and Th17 cell responses aggravate mitochondrial dysfunction and oxidative stress. These joint signals activate and proliferate resident cardiac fibroblasts to differentiate into active myofibroblasts, accelerating Type I/III collagen synthesis and ECM deposition, which leads to terminal dilated cardiomyopathy (DCM). Created in BioRender (https://www.biorender.com/).