Abstract
BACKGROUND: Border disease (BD), caused by Border Disease Virus (BDV), leads to reproductive losses, congenital defects, and persistently infected (PI) lambs that maintain viral circulation. In Iran, existing reports are limited, confined to one area and breed, and rarely integrate clinical, pathological, virological, and genotypic data. This study investigates BD across Iranian sheep breeds, combining clinical observation, pathology, virus detection, and genotype analysis to clarify its epidemiology and support early recognition, targeted control measures, and improved small ruminant health and welfare management nationwide. From 2015 to 2025, a nationwide observational study was conducted in six provinces of Iran to investigate different sheep breeds. Animals showing clinical signs suggestive of BDV underwent thorough clinical examination, with all observations carefully documented, and blood and tissue samples were collected for diagnostic confirmation. Laboratory analyses included serology, molecular detection, virus isolation, genetic characterization (5′-UTR), and pathology. RESULTS: The collected findings were subsequently analyzed to provide a comprehensive understanding of BDV occurrence and characteristics in the studied flocks. Thorough clinical and laboratory examinations confirmed BDV in 234 sheep from various breeds across Iran, including Lacaune, Romanov, Romanov-Sangsari, Torki-Ghashghaei, Shall, and Kordi. Of these, 189 (80.77%) were PI and 45 (19.23%) acutely infected. Tremors (37.2%) were the most frequent sign, followed by brachygnathia (32.9%) and hairy fleece (17.1%), with breed- and region-specific patterns observed. Pigmentation changes occurred only in the Lacaune breed. PI animals showed more severe and diverse clinical signs, though some appeared clinically normal. Genetic analysis revealed clustering within the Konya-like pestiviruses clade (Pestivirus I), closely related to recent Turkish strains (Iran’s western neighbor), suggesting regional circulation or shared sources. CONCLUSIONS: This study, conducted for the first time on such a scale in Iran, provided critical insights into BD, emphasized the diversity of clinical manifestations across different breeds, and addressed the longstanding gap in BDV genotyping. The results offer a valuable foundation for enhancing diagnostic capacity and guiding effective control strategies in Iran and other West Asian countries. Importantly, the findings highlight the previously underrecognized role of BD in Iran and provide clinically relevant evidence that can be applied by veterinarians and researchers in Iran and in other regions with large small-ruminant populations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-026-05293-2.