乙型肝炎病毒X蛋白在体外和体内调节HBV转录和复制的作用和

StephenW

Viruses 2013, 5(5), 1261-1271; doi:10.3390/v5051261

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

StephenW

摘要：B型肝炎病毒（HBV）X蛋白（HBx蛋白）中的调控HBV复制的作用仍存在争议。另外，在本研究中，初步研究HBx在调节HBV复制的作用在HepG2细胞和在体外的Huh7细胞系，瞬时转染系统。接下来，HBx蛋白负责为转录的transactivati​​on的HBV复制和推广的地区，通过一系列体内转染HBx基因的表达质粒HBV复制小鼠模型映射到。在体外设置，HBx蛋白缺乏Huh7细胞对HBV复制的影响不大，但受损的HepG2细胞中HBV的复制。 HBx蛋白在体内设置，产生了强烈的对乙肝病毒的转录和复制的增强作用。对于C-末端三分之二的蛋白质（氨基酸[AA] 51到154）中HBx此功能所需的，跨越一个52至72和88至154的区域被认为是重要的刺激作用HBx蛋白对HBV复制。最后，HBx在HBV复制的调节的作用由宿主细胞类型的影响，和HBx刺激肝细胞在体内的乙肝病毒的转录和复制中具有重要的作用。此外，HBx基因的转录激活功能可能是至关重要的刺激作用，对乙肝病毒的转录和复制。
关键词：B型肝炎病毒的HBx蛋白的转录和复制;细胞培养;鼠标模式