Role and Functional Domain of Hepatitis B Virus X Protein in Regulating HBV Transcription and Replication in Vitro and in Vivo
Dao-Yin Gong 1,2,3,† email, En-Qiang Chen 1,2,† email, Fei-Jun Huang 3,* email, Xiao-Hua Leng 1,2 email, Xing Cheng 1,2 email and Hong Tang 1,2,* email
1 Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China 2 Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China 3 Department of Forensic Pathology, Medical School of Basic and Forensic Sciences, Sichuan University, Chengdu 610041, China † These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 13 March 2013; in revised form: 8 May 2013 / Accepted: 13 May 2013 / Published: 22 May 2013
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.
Keywords: hepatitis B virus; HBx protein; transcription and replication; cell culture; mouse mode 作者: StephenW 时间: 2013-5-23 22:28