Hepatitis B virus x protein induces autophagy via activating death-associated protein kinase

Summary Hepatitis B virus x protein (HBX), a product of hepatitis B virus (HBV), is a multifunctional protein that regulates viral replication and various cellular functions. Recently, HBX has been shown to induce autophagy; however, the responsible mechanism is not fully known. In this study, we established stable HBX‐expressing epithelial Chang cells as the platform to study how HBX induced autophagy. The results showed that the overexpression of HBX resulted in starvation‐induced autophagy. HBX‐induced autophagy was related to its ability to dephosphorylate/activate death‐associated protein kinase (DAPK). The block of DAPK by its siRNA significantly counteracted HBX‐mediated autophagy, confirming the positive role of DAPK in this process. HBX also induced Beclin 1, which functions at the downstream of the DAPK‐mediated autophagy pathway. Although HBX could activate JNK, a kinase known to participate in autophagy in certain conditions, the change in JNK failed to influence HBX‐induced autophagy. In conclusion, HBX induces autophagy via activating DAPK in a pathway related to Beclin 1, but not JNK. This new finding should help us to understand the role of autophagy in HBX‐mediated pathogenesis and thus may provide targets for intervening HBX‐related disorders.