The VP1 protein of foot-and-mouth disease virus: Bridging pathogenicity and control strategies.

The Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen affecting cloven-hoofed animals. Its major structural protein, VP1, serves as a core target that governs viral pathogenicity and the host immune response. The distinctive structure and functions of VP1 are therefore crucial for developing vaccines and effective control strategies. This review systematically examines the multifaceted roles of VP1 in the FMDV life cycle, encompassing RGD motif-mediated viral adsorption, epitope-driven immunomodulation, and mechanisms underlying viral replication and immune evasion. Drawing on recent structural insights from X-ray crystallography and cryo-electron microscopy, we highlight the conformational dynamics of the VP1 G-H loop and its critical role in integrin binding. We also analyse how VP1 genetic variation impacts vaccine efficacy and summarise advances in VP1-based vaccines and diagnostics. Although inactivated vaccines are widely used, their limited cross-protection and cold-chain requirements pose ongoing challenges. Future efforts should integrate artificial intelligence, cross-serotype antigen engineering, and global genetic database mining to create broad-spectrum vaccines and precision diagnostics. This synthesis enhances our understanding of FMDV pathogenesis and offers a framework for improving disease control. The review was conducted following a structured literature synthesis approach, as detailed in the Review Methodology section.