Role of LSDV ORF102 in immune evasion and characterization of ORF102-Deleted recombinant virus

Lumpy skin disease virus is the etiological agent for LSD, a disease that mainly affects cattle with huge economic consequences. Fever, extensive skin lesions, and multiple nodules in various parts of the body of the affected cattle characterize LSD. To date, there have been limited studies on the gene deletion of LSDV, and no research has focused on deleting the LSDV ORF102 gene. Therefore, this study aimed to investigate the role of LSDV ORF102 in immune evasion and to characterize the recombinant virus lacking ORF102. Our results showed that the LSDV ORF102 protein inhibits IFN-β and other interferon-stimulated genes (ISGs). The ORF102 protein suppresses IFN-β expression through the cGAS-STING signaling pathway. Additionally, we generated the recombinant virus (rLSDVΔ102-EGFP) using a three-step virus purification process in cell culture. The growth kinetics of cells infected with the wild-type virus differed slightly from those infected with the recombinant virus. Notably, there is a significant difference in IFN-β and other ISGs expression between cells infected with recombinant virus (rLSDVΔ102-EGFP) and those infected with wild-type LSDV. The study also found that the ORF102 protein interacts with TBK1 but not with cGAS, IRF3, or STING. Overall, this study demonstrates that the LSDV ORF102 protein counteracts IFN-I-mediated antiviral responses by interacting with TBK1. Furthermore, the successful construction of the recombinant virus lacking the ORF102 gene is a critical tool for understanding viral pathogenesis. These findings offer valuable insights into LSDV immune evasion strategies and establish a foundation for the development of a novel, gene-deletion-based vaccine against LSDV.