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

## TL;DR

This study shows how goose astrovirus causes gout by disrupting bile acid metabolism, specifically through the AGXT gene, in infected goslings.

## Contribution

The paper identifies AGXT as a novel driver of gout in GAstV-infected geese through bile acid dysregulation.

## Key findings

- GAstV infection causes multi-organ damage, especially in the kidneys of Jiangnan white goslings.
- Transcriptomic analysis revealed 342 differentially expressed genes, with AGXT significantly upregulated.
- AGXT overexpression is linked to hyperuricemia and gout, offering a new target for poultry breeding.

## Abstract

Goose astrovirus (GAstV) causes fatal gout in goslings, yet the underlying mechanism was unknown. We found that GAstV infection causes multi-organ damage, primarily targeting the kidney. Transcriptomic analysis revealed metabolic dysregulation, specifically an aberrant activation of bile acid metabolism. A key gene within this pathway, AGXT, was significantly upregulated. Since the AGXT enzyme influences uric acid production, its virus-induced overexpression is a likely driver of hyperuricemia and gout. This work unveils a novel metabolic mechanism for GAstV-induced gout, nominating AGXT as a promising target for breeding resistant poultry.

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.