Genomic characterization of the first goat-associated orf virus genome sequenced directly from a human clinical sample in Portugal.

The orf virus (ORFV) is a neglected zoonotic virus, with sporadic human infections, historically identified through clinical suspicion rather than molecular confirmation. We report the first molecularly confirmed human ORFV case in Portugal and the first goat-associated human-derived ORFV genome. Direct hybrid capture sequencing of a clinical biopsy from a veterinary student bitten by a goat yielded a 129.5 kb genome. Phylogenetic analysis placed the isolate within a goat-associated cluster, distinct from the two previously available human-derived genomes. This case highlights the value of molecular surveillance and genomic sequencing for One Health surveillance of neglected zoonoses.