Ecological and Molecular Basis of Capripoxvirus Cross‐Host Transmission: From Transmission Networks to Adaptive Evolution

ABSTRACT Background Capripoxvirus (CaPV), comprising sheeppox virus (SPPV), goatpox virus (GTPV) and lumpy skin disease virus (LSDV), represents a growing transboundary threat to global livestock, with expanding geographic distribution and increasingly prominent cross‐species transmission in mixed farming systems. Objectives This review systematically examines the multifaceted drivers of CaPV spillover from ecological, molecular and evolutionary perspectives. Methods This review integrates ecological, molecular and evolutionary analyses, incorporating mathematical modelling and summarising advances in CRISPR/Cas‐based diagnostics. Results Ecologically, a tripartite network involving habitat sharing, landscape permeability (e.g., forest farmland edges) and arthropod vectors is proposed; mathematical modelling identifies vector‐to‐host ratio and vaccination coverage as critical modulators of outbreak severity. Molecularly, genetic plasticity in terminal genomic regions (e.g., ankyrin family) and host range genes (HRGs) such as M062R, M159, and LSDV012 enable antagonism of host restriction factors including SAMD9, IFIT1 and PKR, with the C7L superfamily playing a pivotal role in breaching species barriers. Evolutionarily, recombination‐driven diversification, immune selection pressure and genetic bottlenecks collectively shape adaptive radiation and frequent host jumping events. Advances in CRISPR/Cas‐based diagnostics are summarised. However, live attenuated vaccines show limitations in safety and efficacy. Conclusions and Clinical Relevance Persistent challenges include ecological surveillance, molecular discrimination of the three species and vaccine–wild type recombination risks. By integrating these disciplines, this review offers a comprehensive framework for understanding CaPV cross‐species transmission and supports the design of precision control strategies targeting ecological and molecular vulnerabilities.