Hepatitis B Virus Disrupts the Blood-Testis Barrier via the Induction of mTOR-Dependent Autophagy in Sertoli Cells

Abstract

Hepatitis B virus (HBV) is one of the most serious public health threats worldwide. HBV is not only able to pass through the blood–testis barrier (BTB); It can also cause impairment of male fertility. However, the mechanisms involved in this process remain unknown. In this study, we showed that HBV can establish persistent infection in human and mouse testes. Persistent HBV infection triggers inflammatory cell invasion, testes immune homeostasis imbalance, and the disruption of the BTB formed by inter-Sertoli cells. HBV mainly persisted in the Sertoli cells and could induce the autophagy of Sertoli cells by HBV X protein (HBx), a major regulatory protein of HBV. Data indicated that the mTOR signal pathway-mediated autophagy plays a pivotal role in HBV-induced BTB damage. Autophagy inhibitor 3-MA and mTOR activator MHY1485 could ameliorate HBV-induced autophagy and BTB damage. These findings demonstrated that the mTOR-mediated excessive autophagy of Sertoli cells induced by HBx could be one of the pathological mechanisms responsible for the fertility decline caused by HBV infection.