Lumpy skin disease (LSD) is a viral disease of cattle that presents with a wide range of clinical outcomes, from mild or subclinical infection to severe disease. We leveraged our work on the cattle study at the Australian Centre for Disease Preparedness (ACDP), CSIRO, to investigate the molecular mechanisms underlying this variability. Peripheral blood mononuclear cells (PBMCs) were collected across multiple post-infection time points and analysed using RNA sequencing to identify transcriptomic signatures associated with resilience and susceptibility.
Differential gene expression analysis revealed clear transcriptomic distinctions between resilient and susceptible animals. The top differentially expressed genes (DEGs) highlighted several immune-related transcripts that were either significantly up- or down-regulated in resilient animals. Principal Component Analysis (PCA) further confirmed the separation between clinical groups, reflecting underlying differences in immune activation and regulation. Functional enrichment analysis pointed to pathways related to antiviral defence, immune signalling, redox balance, and stress response as potential contributors to disease outcome.
Notably, resilient animals exhibited down-regulation of genes associated with cellular stress and interferon-stimulated antiviral responses, suggesting a more balanced and less inflammatory immune strategy. In contrast, several genes involved in redox homeostasis and membrane transport were up-regulated, indicating a possible role for cytoprotective mechanisms in promoting resilience.
These findings reveal novel host transcriptomic patterns that distinguish resilient from susceptible animals in LSDV infection. By highlighting potential biomarkers and regulatory pathways of disease tolerance, this study lays the foundation for the future development of precision vaccines, antiviral interventions, and targeted breeding strategies to enhance natural resilience in cattle.