title: Autophagy required for hepatitis B virus replication in transgenic mice.
abstract: Recent studies indicate that hepatitis B virus (HBV) may induce autophagy to enhance its replication in cell cultures. To understand whether autophagy can indeed enhance HBV replication in vivo, we generated HBV transgenic mice with liver-specific knockout of the Atg5 gene, a gene critical for the initiation of autophagy. Immunoblot analyses confirmed the inhibition of autophagy in the livers of Atg5 knockout mice. This inhibition of autophagy slightly reduced HBV gene expression and affected nuclear localization of the HBV core protein. It also reduced the HBV DNA level in sera by more than 90% and the level of the HBV DNA replicative intermediate in the mouse liver to an almost undetectable level. Our results thus demonstrate that autophagy is important for HBV replication in vivo and raise the possibility of targeting this pathway to treat HBV patients.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033, USA. jamesou@hsc.usc.edu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Tian
authors.forename: Donna
authors.initials: D
authors.lastname: Sir
authors.forename: Cheng-Fu
authors.initials: CF
authors.lastname: Kuo
authors.forename: David K
authors.initials: DK
authors.lastname: Ann
authors.forename: Jing-Hsiung James
authors.initials: JH
authors.lastname: Ou
mesh_terms: D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D004279:DNA, Viral / Q000097:blood; D006515:Hepatitis B virus / Q000472:pathogenicity*; D008099:Liver / Q000821:virology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000172:deficiency; D044967:Serum / Q000821:virology; D019562:Viral Load; D014779:Virus Replication
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D004279:DNA, Viral; D008869:Microtubule-Associated Proteins