Porcine hemagglutinating encephalomyelitis virus induces atypical autophagy via opposite regulation of expression and nuclear translocation of transcription factor EB

•PHEV infection decreases TFEB expression.•PHEV infection activates TFEB by inhibiting MTORC1 activation.•PHEV replication is dependent on TFEB expression. Porcine hemagglutinating encephalomyelitis virus (PHEV) displays neurotropism and induces atypical autophagy. However, the exact mechanisms mediating autophagy induced by PHEV remains uncharacterized. Transcription factor EB (TFEB) is a master transcriptional regulator playing a key role in autophagy and its activity is regulated by MTORC1 kinase on the surface of lysosomes. We first found that PHEV infection decreases TFEB expression, while it activates TFEB by inhibiting MTORC1 activation, indicating that TFEB plays a complex role in the process of PHEV-induced autophagy through opposite regulation of its expression and activity. Furthermore, this study preliminarily demonstrated that PHEV replication is dependent on TFEB expression.