Equine Sarcoid: From BPV-Driven Oncogenesis to Host-Sustained Tumor Persistence

Equine sarcoid is the most common cutaneous neoplasm of equids and represents a distinctive model of virus-associated tumor persistence. Although bovine papillomaviruses, particularly BPV-1 and BPV-2, are recognized as the main etiological agents, viral infection alone does not fully explain the clinical heterogeneity, frequent recurrence, and limited spontaneous regression of these lesions. This review summarizes current evidence on the molecular and cellular mechanisms underlying equine sarcoid pathogenesis, with emphasis on the interaction between BPV infection, host signaling pathways, tumor microenvironment dynamics, and multi-omic evidence of host regulatory networks. BPV oncoproteins, especially E5, promote fibroblast transformation through PDGFβR activation, downstream PI3K/AKT, MAPK and p38 signaling, altered cell survival, and immune evasion mediated by impaired antigen presentation. However, sarcoid persistence appears to depend on broader host-driven processes, including extracellular matrix remodeling, activated fibroblastic and myofibroblastic phenotypes, chronic inflammatory signaling, and ineffective immune clearance. Recent transcriptomic and epigenomic studies further indicate that long non-coding RNAs, DNA methylation changes, circulating microRNAs, and recently identified virus–host chimeric transcripts may contribute to stabilization of the neoplastic phenotype and may represent future biomarkers. Overall, this review proposes a virus-initiated, host-sustained conceptual framework for equine sarcoid pathogenesis, in which viral oncogene activity and host tissue reprogramming cooperate to promote lesion persistence, recurrence, and therapeutic resistance.