Host immune response to lumpy skin disease virus.

Lumpy skin disease virus (LSDV) is a transboundary pathogen of cattle characterised by necrotic skin nodules, lymphadenopathy, and fever. First detected in southern Africa a century ago, it has continued to spread and cause significant welfare concerns and economic losses in Asia and, more recently, in Europe. LSDV replicates locally in the skin before dissemination via lymph and blood, causing vasculitis and characteristic cutaneous lesions. Localised innate immune responses lead to infiltration of immune cells in the skin; however, virally encoded proteins interfere with the innate response's ability to contain infection. Adaptive immunity involves T-cell-mediated IFN-γ responses and production of neutralizing antibodies (nAbs) that are essential for viral clearance. Host factors such as breed, age, and physiological status influence susceptibility and disease severity. Early transcriptomic studies have identified immune gene signatures associated with resilience or severity of disease outcomes. Correlates of protective immunity remain undefined, and the mechanisms of viral immune evasion in vivo are still poorly characterized. While live-attenuated vaccines provide robust protection, potential vaccine-induced reactions and the lack of DIVA-compatible (Differentiating Infected from Vaccinated Animals) diagnostics highlight the need for next-generation platforms. A deeper characterization of the host-LSDV immune interface is therefore critical for developing targeted antivirals and improving global outbreak preparedness. Despite the long history of the disease, the host immune response remains poorly understood, limiting the development of early diagnostics, vaccines, selective breeding strategies, and improved control measures. In this review, we summarize current knowledge of LSDV, highlighting recent advances and key knowledge gaps in disease pathogenesis and the host-virus immune interface.