Coxsackievirus infection and type 1 diabetes: a narrative review of the epidemiological and pathogenic evidence and prevention perspectives

Abstract

Introduction: Type 1 diabetes mellitus (DM1) is an autoimmune disease characterized by the destruction of pancreatic β-cells. Although genetic predisposition is a key factor, the rapid changes in incidence worldwide suggest a major role for environmental triggers. Among them, enterovirus infection—particularly Coxsackie virus B (CVB)—has been consistently associated with the onset of DM1. Objective: To review the epidemiological, pathogenic, and histopathological evidence linking CVB infection to DM1, and to discuss future preventive perspectives through vaccine development.

Methods: A narrative literature search was conducted in PubMed, Embase, Medline, and Google Scholar, including systematic reviews, meta-analyses, cohort studies, clinical trials, and recent publications (1969–2025) assessing the association between enteroviruses and DM1. Results: Epidemiological evidence supported by meta-analyses shows that CVB infection significantly increases the risk of islet autoimmunity (OR 2–4) and clinical DM1 (OR 7–10), with the strongest association observed in the peri-diagnostic period (OR 16). Prospective cohort studies (TEDDY, DIPP) confirmed that enterovirus infection precedes the appearance of islet autoantibodies. Proposed pathogenic mechanisms include direct β-cell cytolysis, persistent low-grade infection, bystander activation of autoreactive lymphocytes, and molecular mimicry. Histopathological studies have detected viral antigens within pancreatic islets, and in some cases, isolation of viable CVB from human pancreatic tissue. Recently, the multivalent CVB vaccine candidate PRV-101 demonstrated safety and immunogenicity in a phase 1 clinical trial, providing proof-of-concept for primary prevention of DM1. Conclusions: The convergence of epidemiological, experimental, and histopathological evidence strongly suggests a relevant and consistent role for CVB in DM1 pathogenesis. The development of CVB vaccines represents a promising strategy for the primary prevention of DM1 in genetically at-risk populations.