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

## TL;DR

This study explores the genetic diversity and host range of Orf virus, revealing it as a generalist pathogen with signs of specialization in sheep and goats.

## Contribution

The study provides new insights into the phylodynamics and host-specific patterns of Orf virus using a global dataset including understudied regions.

## Key findings

- ORFV shows greater genetic variability than previously reported, especially in the VIR gene.
- Signs of host-specific adaptation are observed in sheep and goats, but not in other ruminants or humans.
- Infections in non-core hosts are likely due to habitat overlap and sporadic transmission.

## Abstract

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 host-specific 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.