title: Hepatitis B virus dampens autophagy maturation via negative regulation of Rab7 expression.
abstract: Hepatitis B virus (HBV) infection brings a huge challenge for medical health practitioners. It has been reported that invaded HBV escapes autophagic degradation through inhibiting lysosome maturation following enhanced autophagy formation, which putatively contributes to HBV replication and infection. However, the underlying mechanism by which HBV escapes from autophagic degradation remains elusive. In this study, we monitored the autophagic process using HepG2 cells and mice without or with transient HBV DNA plasmid transfection (pHepG2) or stable HBV infection (HepG2.2.15 cells) in vitro and in vivo. The results of Western blot, transmission electron microscopy and confocal microscopy, confirmed that HBV induced autophagy, while the fusion of autophagosomes with lysosomes was arrested. Furthermore, Rab7, a small GTPase that functions as a molecular switch responsible for the autophagosome-lysosome fusion, was inhibited, suggesting a potential mechanism for HBV-induced inhibition of autophagic degradation. In conclusion, our study proposes a potential mechanism for how HBV escapes autophagic degradation, which might be a novel therapeutic target for controlling HBV infection.
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine.
authors.forename: Tianhui
authors.initials: T
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Jin
authors.forename: Yongsen
authors.initials: Y
authors.lastname: Ding
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
authors.forename: Shiqian
authors.initials: S
authors.lastname: Huang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Congfeng
authors.initials: C
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000502:physiology / Q000821:virology; D001343:Autophagy; D004279:DNA, Viral / Q000502:physiology; D015536:Down-Regulation; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D004279:DNA, Viral; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse; D020691:rab GTP-Binding Proteins