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At present, there is no efficient vaccine or targeted therapy for this virus, primarily because of the unclear pathogenesis of ASF virus (ASFV) infection and its interactions with host responses. Here, we established an oral infection model of ASFV in Landrace pigs and identified gene expression and metabolic changes in the pig spleen following ASFV infection using transcriptomic and metabolomic analyses. After ASFV SY\u20101 infection, 5556 differentially expressed genes (DEGs) were identified, wherein 2577 and 2979 were upregulated and downregulated, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that these genes were dynamically enriched in various biological processes, including the innate immune response, inflammatory response, chemokine signaling, and signal transduction. Integrated transcriptome and metabolome analyses indicated that ASFV altered diverse pathways, including cysteine and methionine metabolism, cGMP\u2010PKG signaling, choline metabolism in cancer, cholesterol metabolism, sphingolipid signaling, protein digestion and absorption, FoxO signaling, and central carbon metabolism in cancer. Additionally, we confirmed that metabolites, such as L\u2010glutamate, glycerophosphocholine, and L\u2010serine, significantly inhibit ASFV proliferation in vitro. This study improves our comprehension of the relationships between viruses and hosts, and it serves as a guide for identifying new inhibitors for ASFV.<\/jats:p>","DOI":"10.1155\/tbed\/2453420","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T10:05:27Z","timestamp":1752487527000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Infection Characteristics, Transcriptomics, and Metabolomics of African Swine Fever Virus SY\u20101 Strain in Orally Infected Weaned Landrace 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