Lumpy skin disease virus replication kinetics and local immune host response in a novel bovine skin explant model

Lumpy skin disease (LSD) is an emerging disease of cattle that has spread from Africa into the Middle East, Asia and Europe. It is caused by lumpy skin disease virus (LSDV), a poxvirus that causes significant economic and animal welfare concerns in diseased animals. Despite its global significance, the pathogenesis of LSD, particularly at the skin interface, where the disease’s characteristic lesions occur, remains poorly understood.

Skin explant models are well established in human research, as they provide a more physiologically relevant platform than cell monolayers. Their application in veterinary research, however, remains underexplored. We established and optimised a bovine full-thickness skin explant model that was inoculated with a vaccine-like recombinant LSDV strain (Clade 2.5) at approximately 10³ TCID₅₀ and cultured for up to 6 days. Initial analysis using both TCID₅₀ and qPCR confirmed that the explants supported productive LSDV replication, demonstrating their suitability as a biologically relevant model. The amount of LSDV viral genome copies increased tenfold compared to the initial inoculum over 6 days. Viral antigen was detected by immunohistochemistry 6 days post-inoculation. Viral antigen distribution and host response markers were also analysed. This ex vivo model provides the opportunity to characterise viral tropism, replication kinetics, pathogenesis and local immune responses in skin tissue.

To our knowledge, this represents the first use of bovine skin explants to study a viral pathogen. Beyond providing novel insights into LSDV biology, this model provides a platform for investigating LSDV in wildlife species, evaluating vaccines and antivirals, and researching other skin-tropic viruses. With LSDV continuing to spread internationally, this system provides a unique opportunity to advance our understanding of poxvirus pathogenesis and to develop new strategies to mitigate skin-tropic viral infections.