AGXT-Driven Bile Acid Dysregulation Triggers Viral Gout in Astrovirus-Infected Jiangnan White Geese.

Goose astrovirus (GAstV) infection has emerged as a prevalent cause of urate deposition and viral gout in major goose farming across China, leading to high mortality and substantial economic losses. However, the molecular mechanisms linking GAstV to gout pathogenesis remain elusive. Here, a total of 10 five-day-old Jiangnan white goslings were selected, and tissue damage and kidney gene expression profiles were investigated. The results showed multi-organ damage in GAstV-infected gosling, including kidney, liver, spleen, and lung. Also, 342 differentially expressed genes were identified in infected kidney tissues after 10 days post-infection using transcriptomic sequencing, including 185 upregulated and 157 downregulated genes. In addition, gene set enrichment analysis revealed significant positive correlations between GAstV infection and bile acid metabolism and fatty acid metabolism pathways. Notably, bile acid metabolism was implicated in uric acid regulation and gout progression. Protein-protein interaction network analysis identified AGXT as a central hub gene within the bile acid metabolic pathway, with key upregulated interactors including PIPOX, ALDH1A1, and CAT. AGXT, a critical enzyme in glyoxylate detoxification, directly modulates uric acid biosynthesis. Our findings propose that GAstV-induced activation of bile acid metabolism, particularly AGXT upregulation, drives hyperuricemia and subsequent gout pathology. This study elucidates a novel mechanism of GAstV-associated metabolic dysregulation and provides actionable genetic targets for antiviral breeding strategies in waterfowl.