Coxsackie B Virus-Induced Autoimmunity in Type 1 Diabetes Mellitus: Mechanisms and Emerging Prevention Strategies

Abstract

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder characterized by the progressive destruction of pancreatic beta cells. Coxsackie B Virus (CVB), particularly CVB1, CVB3, and CVB4, has been identified as a key environmental trigger in the pathogenesis of T1DM, particularly in genetically predisposed individuals. This narrative review synthesizes two decades of evidence (2005–2025) to explore the mechanisms by which CVB contributes to autoimmunity and emerging prevention strategies. CVB induces beta cell autoimmunity through molecular mimicry, bystander activation, and persistent viral infections that promote chronic inflammation and immune-mediated beta cell damage. Specific serotypes, such as CVB3 and CVB4, have been shown to have stronger associations with T1DM onset, emphasizing the importance of targeted interventions for these serotypes. Recent advancements in prevention strategies include multivalent CVB vaccines, antiviral agents such as pleconaril, and immune-modulating therapies like tolerogenic vaccines and regulatory T cell (Treg) expansion. However, challenges remain regarding their safety, timing of administration, and immune cross-reactivity. Early diagnostic efforts focused on biomarkers such as CVB-specific antibodies, islet autoantibodies (e.g., GAD65, ICA, ZnT8), and HLA risk alleles are crucial for identifying individuals in the latent phase of T1DM. To mitigate the risk of CVB-induced T1DM, an integrated public health approach—combining virological surveillance, vaccination campaigns, and early immunological screening—is essential. We recommend prioritizing longitudinal cohort studies, the development of safe multivalent vaccines, and investment in community-based early detection programs. A collaborative, multidisciplinary approach is vital to prevent or delay T1DM onset in at-risk populations