Role and functional domain of hepatitis B virus X protein in regulating HBV transcription and replication in vitro and in vivo.

Role and functional domain of hepatitis B virus X protein in regulating HBV transcription and replication in vitro and in vivo.
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DOI:
10.3390/v5051261
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发表时间:
2013-05-22
期刊:
Viruses
影响因子:
--
通讯作者:
Tang H
Tang H
中科院分区:
其他
文献类型:
--
作者:
Gong DY;Chen EQ;Huang FJ;Leng XH;Cheng X;Tang H

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乙肝病毒X蛋白(HBx)在调节乙肝病毒复制中的作用仍存在争议。在本研究中,我们利用瞬时转染法初步研究了HBx在体外培养的HepG2和HuH7细胞中对乙肝病毒复制的调控作用。接下来,通过体内转染一系列HBx表达载体,在一个HBx复制小鼠模型中定位了HBx负责转录反式激活和促进HBx复制的区域。在体外实验中,HBx缺乏对Huh7细胞中的乙肝病毒复制几乎没有影响,但对HepG2细胞中的乙肝病毒复制有抑制作用。在体内实验中,HBx对乙肝病毒的转录和复制有很强的促进作用。对于C-末端,HBx的这一功能需要三分之二的蛋白质(氨基酸[AA]51到154),跨越AA 52到72和88到154的区域被发现对HBx刺激HBx复制的功能是重要的。综上所述,HBx在乙肝病毒复制调控中的作用受宿主细胞类型的影响,HBx在体内对肝细胞内的乙肝病毒转录和复制具有重要的刺激作用。此外,HBx的转录反式激活功能可能是其刺激乙肝病毒转录和复制的关键。
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.
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发表时间: 2012-05
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