Dual analysis of wild-type and attenuated and host cell transcriptomes revealed novel virus-host cell interactions.

Currently, the only available commercial vaccines for (ORFV) are live attenuated vaccines, which present a potential risk of reversion to virulence. Therefore, understanding the pathogenic mechanisms of different virulent strains of ORFV and host immune responses triggered by these viruses is crucial for developing new vaccines and interventions. In this study, we found that the attenuated strain downregulates the host innate immune response and antiviral activity. In addition, we noted that the wild-type strain can induce the immune response pattern centered on interferon-stimulated genes and interferon regulatory factor gene family. We predicted that STAT1 and STAT2 are the main transcription factors upstream of target gene promoters through gene regulatory networks and exert significant regulatory effects on co-expressed genes. Our study elucidated the complex interaction between ORFV strains and host cell immune responses, providing new insights into vaccine research for ORFV.