Mapping Molecular Determinants of Antigenicity and Pathogenicity of Infectious Bursal Disease Virus (IBDV): A Scoping Review.

Infectious bursal disease virus (IBDV) is an immunosuppressive pathogen posing a major threat to poultry health worldwide. Its marked phenotypic variability is driven by the rapid evolution of its double-stranded RNA genome, primarily achieved through mutation and reassortment. Although extensive evidence has been generated on molecular determinants of antigenicity and pathogenicity, interpretation is often hindered by heterogeneity and lack of systematicity. This scoping review synthesizes over 35 years of research on amino acid positions influencing IBDV phenotype. A total of 62 studies reporting 107 functionally relevant sites were identified and critically appraised based on evidence type, methodological approach, and ability to infer causality. The results confirmed the central role of VP2, particularly its hypervariable region, while also highlighting the increasingly recognized contribution of other viral proteins. Despite good agreement, comparability across studies was limited by substantial heterogeneity in experimental design and the frequent focus on partial genomic regions. Notably, some molecular markers were context-dependent or inconsistently associated with phenotypic outcomes, underscoring the need for proper interpretation of molecular determinants and for more standardized and comprehensive approaches, including full-genome analyses and reverse genetics. Overall, these findings provide a valuable framework for enhancing molecular diagnostics and supporting the rational design of next-generation vaccines.