Genome-wide transcriptome profiling in crossbred pigs after challenge with Classical Swine Fever Virus

The present study aimed to characterize the immune response, differential gene expression, and functional alterations observed following an in vivo challenge of Classical Swine Fever Virus (CSFV) in crossbred pigs. RNA-sequencing was performed on whole blood samples collected from three pigs before and at 7 days post-infection. A total of 3428 differentially expressed genes (DEGs) were identified, including 970 significantly upregulated and 261 downregulated genes (|log₂ fold change| ≥ 1.5, adjusted p < 0.05). The most prominent DEG was LAMB4, a gene associated with cellular attachment receptors facilitating CSFV binding to porcine cells. Several cytokine-cytokine receptor interaction genes, such as CXCL12, CCL2, CCR1, and IL10RA, were upregulated, indicating a strong activation of innate immune responses. Simultaneously, multiple adaptive immune genes, including CD28, CD83, SLA-DQB1, and IL1A, IL12A, IL26 were downregulated, suggesting viral-mediated suppression of antigen presentation and T-cell signaling. Pathway analysis highlighted the involvement of platelet activation and coagulation cascades during viral evasion. Protein-protein interaction (PPI) analysis revealed a core antiviral module comprising MX1, MX2, ISG15, IFIH1, OASL, IFIT1, and UBE2L6, which are central to interferon signaling and viral restriction. Transcription factors such as ETV7, TOX3, and MSC were upregulated, pointing to immune modulation and possible T-cell exhaustion. Conversely, downregulation of HES1, PRDM6, and MYOG indicated impaired lymphocyte differentiation and tissue repair. Overall, the findings suggest a dual host response to CSFV, with strong innate activation alongside adaptive immune suppression, providing valuable insights for vaccine and therapeutic development.