Unravelling the Evolutionary Complexity of Orf Virus: A Global and Multi-Host Perspective

Orf virus (ORFV), a member of the Parapoxvirus genus, is commonly associated with a highly infectious skin disease primarily affecting sheep and goats, with a reported zoonotic potential. Initially identified in the 18th century, ORFV has been sporadically reported in other species, including humans. The present study analyzed the genetic variability and phylodynamic patterns of ORFV using the highly variable VIR gene, focusing on global strains from multiple hosts, including various species of ruminants and humans. A dataset of 267 ORFV strains from around the world, including sequences from the understudied island of Cuba, was used for the analyses. Results revealed greater genetic variability for ORFV than previously reported. While the virus may be defined as a generalist pathogen, capable of infecting various ruminant species and less frequently humans, signs of hostspecific specialization are emerging exclusively for sheep and goats. Other ruminant species and humans may be categorized as occasional hosts, with infections likely linked to habitat overlap with sheep and goats and sporadic transmission that appears influenced by specific risk factors. In conclusion, these findings contribute to a better understanding of the transmission risks posed by ORFV, highlighting the need for further investigations into its potential to infect a broader range of hosts, particularly humans.