Host-Orf virus interactions: A comprehensive review of pathogenesis and immune evasion mechanisms

Orf virus (ORFV), a zoonotic parapoxvirus, causes contagious ecthyma in small ruminants. It is uniquely characterized by its ability to cause proliferative, self-resolving skin lesions and systematically evade host immunity to cause repeated infections. This review provides an in-depth analysis of ORFV pathogenesis, focusing on viral entry, replication, and lesion development. Furthermore, we highlight the sophisticated immune evasion strategies employed by ORFV that enable it to thrive as a pathogen. By integrating recent molecular and immunological advances, we illustrate how key viral immunomodulatory proteins systematically subvert innate and adaptive host defenses, including interferon pathways, NF-κB signaling, and apoptosis. Deciphering these complex virus-host interactions not only clarifies ORFV's evolutionary success but is also critical for designing effective vaccines and novel therapeutics.