title: Successful establishment and evaluation of a new animal model for studying the hepatitis B virus YVDD mutant.
abstract: The treatment of infection with lamivudine-resistant mutants of hepatitis B virus (HBV) with mutations in the YMDD motif has become a crucial issue in the clinic. In this work, the plasmids pcDNA3.1 (+)-HBV/C-YVDD and pcDNA3.1 (+)-HBV/C-YMDD were constructed and injected into BALB/c mice using a hydrodynamics-based procedure to investigate viral replication and expression of HBV lamivudine-resistant YVDD mutants in vivo. Compared with the YMDD group, HBsAg levels were higher in sera of mice in the YVDD group, but HBeAg levels were lower on day 1 after injection. Levels of HBcAg in hepatocytes were higher in the YVDD group on day 1, whereas the HBsAg levels were lower. The levels of HBV mRNA in the liver were higher in mice in the YVDD group on day 1 after injection. The results showed that injection with these plasmids resulted in efficient initiation of replication of HBV in mice and also suggested that the combined mutations in YVDD mutants could affect the replication process.
authors.affiliation: Department of Microbiology, The Heilongjiang Key Laboratory of Immunity and Infection, Pathogenic Biology, Harbin Medical University, 157 Baojian Road, Nangang, Harbin, Heilongjing, 150081, China.
authors.forename: Yan-Xiu
authors.initials: YX
authors.lastname: Ma
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Song
authors.forename: Xu
authors.initials: X
authors.lastname: Teng
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Fu
authors.forename: Mei-Li
authors.initials: ML
authors.lastname: Hao
authors.forename: Si-Jia
authors.initials: SJ
authors.lastname: Chen
authors.forename: Wei-Zhen
authors.initials: WZ
authors.lastname: Xu
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Gu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006509:Hepatitis B / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000302:isolation & purification; D006513:Hepatitis B e Antigens / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000235:genetics*; D006524:Hepatitis, Viral, Animal / Q000821:virology*; D008099:Liver / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D013047:Specific Pathogen-Free Organisms
chemical_list: D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase