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HBV is not only able to pass through the blood\u2013testis 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\u2010Sertoli 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\u2010mediated autophagy plays a pivotal role in HBV\u2010induced BTB damage. Autophagy inhibitor 3\u2010MA and mTOR activator MHY1485 could ameliorate HBV\u2010induced autophagy and BTB damage. These findings demonstrated that the mTOR\u2010mediated excessive autophagy of Sertoli cells induced by HBx could be one of the pathological mechanisms responsible for the fertility decline caused by HBV infection.<\/jats:p>","DOI":"10.1096\/fj.202403422r","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T10:34:31Z","timestamp":1745404471000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hepatitis B Virus Disrupts the Blood\u2010Testis Barrier via the Induction of\n                    <scp>mTOR<\/scp>\n                    \u2010Dependent Autophagy in Sertoli Cells"],"prefix":"10.1096","volume":"39","author":[{"given":"Jingyao","family":"Lian","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, 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