Emergence of foot-and-mouth disease virus SAT 1 topotype III in Iran: molecular and phylogenetic analysis.

Foot-and-mouth disease (FMD) is one of the most devastating viral diseases affecting cloven-hoofed livestock, leading to significant economic losses. Among the seven established serotypes of this disease, three (O, A, and Asia 1) have been continuously reported and are routinely included in the vaccination schedule in Iran. In response to a severe, atypical FMD outbreak that emerged in October 2025, we collected clinical samples from affected cattle and sheep. We conducted RT-PCR, sequenced the products, and subsequently performed phylogenetic analysis of the viral sequences against all available global topotypes to determine the origin of the incursion. We identified the causative agent as a SAT 1 serotype, a strain not included in the Iranian vaccination schedule. Phylogenetic analysis revealed that the Iranian strains cluster within topotype III, indicating the closest evolutionary relationship to Botswana isolates. This study provides the first definitive evidence of the emergence and transmission of FMDV SAT 1/III in Iran, posing a severe threat to regional livestock industries, which mandates an urgent reassessment of current FMD surveillance and vaccine strategies and highlights a significant new risk across the Middle East region. The unexpected emergence of this lineage necessitates further investigation into the source of the incursion, with potential pathways including laboratory-derived origins or the use of contaminated or incompletely inactivated vaccines.