慢性乙型肝炎病毒（HBV）感染仍然是全球公共卫生关注的主要问题之一，它会发展成为肝纤维化、肝硬化和肝细胞癌。最近的证据表明，内体和自噬泡对HBV复制是有益的。然而，目前尚不清楚HBV如何利用这些细胞内泡系统进行复制。RAB5A是小GTP酶家族的成员，在早期内体生成和自噬启动中起着关键作用。我们观察到，与乙型肝炎病毒表达的肝血管瘤细胞系以及慢性HBV感染患者的肝组织样本相比，RAB5A的mRNA和蛋白水平显著增加。此外，RAB5A沉默显著抑制了乙型肝炎病毒在转染和感染的肝血管瘤细胞中的复制和亚病毒颗粒（SVP）表达，而RAB5A过表达则增加了它们的表达。在机制上，RAB5A通过与EEA1相互作用增强早期内体（EE）-晚期内体（LE）激活，同时通过与VPS34相互作用增强自噬诱导。此外，HBV感染增强了RAB5A介导的EE-LE系统和自噬的双重激活。综上所述，我们的研究结果强调了HBV利用RAB5A介导的内体和自噬泡通路的双重激活进行复制和持久性的过程。因此，RAB5A是慢性HBV感染治疗的潜在靶点。

Chronic hepatitis B virus (HBV) infection remains one of the major global public health concerns, and it develop into liver fibrosis, cirrhosis, and hepatocellular carcinoma. Recent evidence suggests that endosomal and autophagic vesicles are beneficial for HBV replication. However, it has not been well elucidated how HBV exploits such intracellular vesicle systems for its replication. RAB5A, a member of small GTPase family, plays crucial roles in early endosome biogenesis and autophagy initiation. We observed that RAB5A mRNA and protein levels were significantly increased in HBV-expressing hepatoma cell lines as well as in liver tissue samples from chronic HBV-infected patients. Moreover, RAB5A silencing inhibited HBV replication and subviral particle (SVP) expression significantly in HBV-transfected and -infected hepatoma cells, whereas RAB5A overexpression increased them. Mechanistically, RAB5A increases HBV replication through enhancement of early endosome (EE) - late endosome (LE) activation by interacting with EEA1, as well as enhancing autophagy induction by interacting with VPS34. Additionally, HBV infection enhances RAB5A-mediated dual activation of EE-LE system and autophagy. Collectively, our findings highlight that HBV utilizes RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways for its own replication and persistence. Therefore, RAB5A is a potential target for chronic HBV infection treatment.