Abstract

Goose astrovirus (GAstV) is a newly identified avian pathogen that causes fatal gout in goslings, characterized by kidney damage and high mortality. Unlike non-pathogenic human gout, GAstV-induced gout lacks reference models due to the absence of goose-derived cell lines and standard experimental animals, limiting mechanistic studies. Here, primary goose kidney organoids (GKOs) were isolated from 28-day-old goose embryos. GKOs retained physiological structures and functions comparable to in vivo kidneys. GAstV infection in GKOs was evaluated across renal cell lineages and compared with in vivo outcomes. Viral replication and effects on uric acid metabolism were assessed at different multiplicities of infection. GAstV readily infected GKOs, targeting progenitor, pluripotent stem, collecting duct, and renal tubular cells, consistent with in vivo findings. At a multiplicity of infection of 10.0, GAstV rapidly induced a significant elevation of uric acid, whereas lower doses had weaker effects, paralleling disease severity in goslings. In contrast, GAstV replication was minimal in 2D cells, and other avian viruses failed to induce uric acid elevation in GKOs. Post-infection, transcriptomic and metabolomic analysis showed GAstV remodeled global gene expression and metabolism, mainly disrupting purine metabolism pathways. GAstV infection significantly increased mRNA levels of SLC22A23, SLC17A5, and SLC13A3, which were correlated positively with uric acid. GKOs provide a physiologically relevant model for elucidating GAstV pathogenesis, offering new insights into virus-induced gout and a platform for studying goose viral diseases.