title: Biological characteristics of the rtA181T/sW172* mutant strain of Hepatitis B virus in animal model.
abstract: BACKGROUND
  The effects of Hepatitis B virus (HBV) rtA181T/sW172* mutation on viral replication and pathogenicity was concerned recently. This study aimed to investigate the biological characteristics of rtA181T/sW172* mutant strain of HBV in animal model.
  
  
  METHODS
  The rtA181T/sW172* mutant plasmid was constructed using the pHBV4.1 (wild type HBV) as a template. The wild and mutant HBV replication mouse models were established utilizing a hydrodynamic technique. The titers of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, and HBV DNA in serum, and the levels of HBsAg, hepatitis B core antigen(HBcAg), HBV DNA replication intermediates (HBV DNA RI) and HBV RNA in liver were measured after 1, 3, 5, 7, 10, 12 and 15 days of plasmid injection.
  
  
  RESULTS
  In wild-type HBV replication mouse model, serum HBsAg was high on day 1, 3, and 5, but became lower since day 7; while in mutant HBV mouse model, serum HBsAg was always at very low level. In liver tissues, HBV DNA RI of wild type HBV was detected on day 1 after transfection. The level subsequently peaked on day 3, gradually declined after day 5, and was almost undetectable on day 10. However, the HBV DNA RI levels of the mutant strain were always higher and lasted longer until day 15. Consistently, the expression levels of HBsAg and HBcAg in liver of the mutant group were significantly increased.
  
  
  CONCLUSIONS
  In the case of the HBV rtA181T/sW172* mutation, the secretion of serum HBsAg was impaired, whereas HBV DNA replication and HBsAg/HBcAg expression were increased in liver. These results suggest that the mutation can impair HBsAg secretion, and may cause the accumulation of viral core particles in liver.
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dai
authors.forename: En-Qiang
authors.initials: EQ
authors.lastname: Chen
authors.forename: Lang
authors.initials: L
authors.lastname: Bai
authors.forename: Dao-Yin
authors.initials: DY
authors.lastname: Gong
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Zhou
authors.forename: Xing
authors.initials: X
authors.lastname: Cheng
authors.forename: Fei-Jun
authors.initials: FJ
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000473:pathology* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity*; D008099:Liver / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020125:Mutation, Missense; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D012194:RNA-Directed DNA Polymerase