GoAstV Induced Mitophagy and Ferroptosis in the Spleen of Goslings.

A novel goose astrovirus (GoAstV) has emerged in various provinces of China, leading to a mortality rate of up to 50% among GoAstV goslings. The spleen is an important immune organ in geese. Studies have shown that goslings infected with GoAstV exhibit higher viral loads in their spleens, and the spleens sustain damage. However, the mechanism underlying its induction of spleen injury remains to be elucidated. Therefore, a gosling infection model with GoAstV was established in this experiment. The Con group was subcutaneously injected with 0.2 mL of saline, while the GoAstV group was subcutaneously injected with GoAstV JX01 (2 × 106 TCID50/0.2 mL). Spleen tissues were collected on days 1, 3, 6, 9 post-infection (dpi). The results showed that the body weight of the GoAstV group decreased significantly, while the spleen weight and spleen index increased significantly. Post-mortem examination revealed that the spleen of the GoAstV group was significantly enlarged. The viral load in the spleen reached its peak at 6 dpi. Histopathological and electron microscopy revealed lymphocyte necrosis, autophagic lysosomes, and mitochondria autophagosomes. The spleen of the GoAstV group exhibited increased iron content, elevated malondialdehyde (MDA) production, decreased glutathione (GSH) content, and reduced glutathione peroxidase (GSH-Px) activity. RT-qPCR and Western blot analyses revealed that GoAstV upregulated mRNA expression of pro-inflammatory cytokines and inhibited anti-inflammatory cytokines. GoAstV also upregulated genes and proteins linked to ferroptosis and mitophagy, while downregulating those associated with anti-ferroptosis and SQSTM1. In conclusion, our findings suggest that GoAstV infection may induce mitophagy and ferroptosis in the gosling spleen, thereby contributing to splenic injury.