Sequence analysis and functional characterization of full-length hepatitis B virus genomes from Korean cirrhotic patients with or without liver cancer.
Sequence analysis and functional characterization of full-length hepatitis B virus genomes from Korean cirrhotic patients with or without liver cancer.
复制标题
患有或不患有肝癌的韩国肝硬化患者全长乙型肝炎病毒基因组的序列分析和功能表征
DOI：
10.1016/j.virusres.2017.03.021
复制
发表时间：
2017-05-02
期刊：
影响因子：
5
通讯作者：
Tong S
中科院分区：
文献类型：
--
作者：
Zhou H;Gewaily D;Ahn SH;Preskill C;Wang Y;Zong L;Zhang J;Han KH;Wands J;Li J;Tong S
本研究的目的是确定和表征与晚期肝病相关的B型肝炎病毒（HBV）基因组突变。从18名患有或不患有肝细胞癌（HCC）的韩国患者的血清中扩增C2亚型的3.2kb HBV基因组，并通过人肝癌细胞中的瞬时转染实验对每个患者的两个克隆进行表征。虽然A1762 T/G1764 A核心启动子突变在两组中都很普遍，但G1896 A前C区突变消除了B e抗原（HBeAg）表达在HCC克隆中更常见（55% vs. 20%）。高复制能力主要见于HCC克隆，并与核心启动子突变相关，而更多的非HCC克隆含有无功能的核心基因（34%对8%）。在60%的HCC克隆和38%的非HCC克隆中发现了preS区域的大的框内缺失。他们去除了大包膜蛋白的前11个残基，或削弱了小包膜蛋白的表达，或删除了preS 2结构域中的中和表位。额外的点突变阻止了中包膜蛋白的表达，或导致preS或S区域中的无义突变以截短大和/或小包膜蛋白。因此，许多克隆不能表达或分泌B型肝炎表面抗原（HBsAg）。总之，与慢性HBV感染晚期相关的突变是复杂多样的。宿主免疫压力最有可能选择HBV基因组突变，以消除或减少HBeAg或HBsAg的产生，增强基因组复制，或逃避中和抗体。这些突变中的一些可能有助于肝硬化或HCC的发展。
This study aimed to identify and characterize mutations in the hepatitis B virus (HBV) genome associated with advanced liver diseases. The 3.2-kb HBV genome of the C2 subgenotype was amplified from sera of 18 cirrhotic Korean patients with (10) or without (8) hepatocellular carcinoma (HCC), and two clones per patient were characterized by transient transfection experiments in human hepatoma cells. While A1762T/G1764A core promoter mutations were highly prevalent in both groups, the G1896A precore mutation to abolish hepatitis B e antigen (HBeAg) expression was more common in HCC clones (55% vs. 20%). High replication capacity was mostly found in HCC clones and associated with core promoter mutations, whereas more non-HCC clones harbored a nonfunctional core gene (34% vs. 8%). Large in-frame deletions in the preS region were found in 60% of HCC clones and 38% of non-HCC clones. They removed the first 11 residues of large envelope protein or impaired small envelope protein expression, or deleted a neutralizing epitope in the preS2 domain. Additional point mutations prevented middle envelope protein expression, or caused nonsense mutations in the preS or S region to truncate large and/or small envelope protein. Consequently, many clones were unable to express or secrete hepatitis B surface antigen (HBsAg). In conclusion, mutations associated with the advanced stage of chronic HBV infection are complex and diverse. Host immune pressure most likely selected for mutations in the HBV genome to abolish or reduce HBeAg or HBsAg production, to enhance genome replication, or to escape neutralizing antibodies. Some of these mutations may contribute to liver cirrhosis or HCC development.
登录
查看更多内容
影响因子：
5.4
作者：
NASSAL, M
通讯作者：
NASSAL, M
影响因子：
15.9
作者：
Baumert, TF;Rogers, SA;Liang, TJ
通讯作者：
Liang, TJ
影响因子：
4.6
作者：
Norder, H;Couroucé, AM;Magnius, LO
通讯作者：
Magnius, LO
DOI：
10.1099/vir.0.2008/002824-0
发表时间：
2008-11
期刊：
The Journal of general virology
影响因子：
--
作者：
Fang ZL;Sabin CA;Dong BQ;Wei SC;Chen QY;Fang KX;Yang JY;Huang J;Wang XY;Harrison TJ
通讯作者：
Harrison TJ
影响因子：
29.4
作者：
Kao, JH;Chen, PJ;Chen, DS
通讯作者：
Chen, DS