Dynamic Gene Network Alterations and Identification of Key Genes in the Spleen During African Swine Fever Virus (ASFV) Infection.

ASFV is responsible for high mortality in domestic pigs and has caused substantial economic impact on the global swine industry due to herd losses, trade restrictions, and disease control measures. We analyzed publicly available spleen RNA-seq data from ASFV-infected pigs (n = 13 total samples), including 7 pre-infection (0 dpi), 4 samples at 2 days post-infection (2 dpi), and 2 samples at 5 dpi (5 dpi). Weighted gene co-expression network analysis (WGCNA) identified 19 modules; module-trait correlations revealed six modules associated with infection time. A co-expression module enriched for innate immune and antiviral response genes was strongly upregulated at 2 dpi, whereas a module enriched for ribosomal, translation, and metabolic process genes was broadly downregulated at 5 dpi. Protein-protein interaction analysis highlighted hub genes, including EPRS1 and USP7 within core cellular/translation programs and CMPK2 and ZBP1 within innate-immune signaling. Collectively, our results provide a network-level view of dynamic host responses and indicate coordinated shifts in immune and metabolic programs over time. These results identify CMPK2, ZBP1, EPRS1, and USP7 as hypothesis-generating hub gene candidates, warranting further validation to establish mechanistic roles and assess potential translational relevance.