title: Role and functional domain of hepatitis B virus X protein in regulating HBV transcription and replication in vitro and in vivo.
abstract: The role of hepatitis B virus (HBV) X protein (HBx) in the regulation of HBV replication remains controversial. In the present study, the role of HBx in regulating HBV replication was initially investigated in both HepG2 and Huh7 in vitro cell lines with a transient transfection system. Next, the regions of HBx responsible for transcriptional transactivation and promotion of HBV replication were mapped in an HBV replication mouse model by in vivo transfection of a series of HBx expression plasmids. In an in vitro setting, HBx deﬁciency had little effect on HBV replication in Huh7 cells, but impaired HBV replication in HepG2 cells. In an in vivo setting, HBx had a strong enhancing effect on HBV transcription and replication. For the C-terminal two-thirds of the protein (amino acids [aa] 51 to 154) was required for this function of HBx, and the regions spanning aa 52 to 72 and 88 to 154 were found to be important for the stimulatory function of HBx on HBV replication. In conclusion, the role of HBx in HBV replication regulation is affected by host cell type, and HBx has an important role in stimulating HBV transcription and replication in hepatocytes in vivo. Further, the transcriptional transactivation function of HBx may be crucial for its stimulatory effect on HBV transcription and replication.
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China. daoyingong@163.com
authors.forename: Dao-Yin
authors.initials: DY
authors.lastname: Gong
authors.forename: En-Qiang
authors.initials: EQ
authors.lastname: Chen
authors.forename: Fei-Jun
authors.initials: FJ
authors.lastname: Huang
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Leng
authors.forename: Xing
authors.initials: X
authors.lastname: Cheng
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D002460:Cell Line; D004252:DNA Mutational Analysis; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication
chemical_list: D050505:Mutant Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein