NIBV Induces Incomplete Autophagy via AMPK‐TFEB, Causing Kidney Injury in Chicks

Nephropathogenic infectious bronchitis virus (NIBV) infection leads to urate deposition in chick kidneys, resulting in severe kidney injury and affecting chicken performance, but its pathogenesis has not been fully elucidated. In this study, we observed a large number of autophagosomes in the kidney tissues and cells of NIBV-infected chicks under electron microscopy, and the proteomics results revealed that AMPK signaling was altered. In the early and late stages of viral infection, the expression of autophagolysosome-related proteins was significantly upregulated, and autophagic flux was unimpeded. However, at the peak of viral infection, the expression of lysosome-related proteins was significantly downregulated in chick kidneys and tubular epithelial cells. Blocked autophagic flux was accompanied by the downregulation of AMPK expression. Therefore, we overexpressed AMPK and found that increased AMPK phosphorylation activated TFEB and promoted its nuclear translocation. Autophagic flux was restored, and NIBV replication was significantly reduced. Overall, this study reveals that NIBV can inhibit the nuclear translocation of TFEB by suppressing the expression of AMPK, leading to the blockade of autophagolysosomal functions, in turn increasing NIBV replication and triggering severe kidney injury in chicks.