Molecular Characterization and Functional Analysis of Occult Hepatitis B Virus Infection in Chinese Patients Infected With Genotype C
Molecular Characterization and Functional Analysis of Occult Hepatitis B Virus Infection in Chinese Patients Infected With Genotype C
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DOI：
10.1002/jmv.21463
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发表时间：
2009-05-01
影响因子：
12.7
通讯作者：
Gu, Hong-Xi
中科院分区：
文献类型：
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作者：
Fang, Yong;Teng, Xu;Gu, Hong-Xi
隐匿性HBV感染被定义为HBV表面抗原（HBsAg）阴性个体中HBV DNA的持续存在，不同国家报道了许多不同的机制。然而，在中国，HBV感染的流行地区之一，尚未发表关于隐匿性HBV感染的报告。本研究探讨了我国隐匿性HBV感染的病毒学特征和发病机制。对8例隐匿性HBV感染者（S1 ~ S8）和3例HBsAg阳性者（SWT 1 ~ SWT 3）的HBV DNA全长进行了克隆和测序。此外，将来自隐匿性病例的四个完整线性HBV基因组瞬时转染到HepG 2细胞中。测序结果显示隐匿性HBV感染患者中存在两种主要突变，如下：前S1（S3，S4和S7）和X（S1，S2和S5）区域缺失。这种缺失涵盖了S启动子和基本核心启动子（BCP），这些变体的功能分析也表明DNA复制和抗原表达的减少。两名隐性感染患者（S6和S8）没有能够干扰主要病毒群体中病毒复制和基因表达的突变。因此，S启动子和BCP区的缺失使调控元件失效可能是HBsAg缺失的原因，多种机制可能是导致隐匿性HBV感染的原因。J. Med. Virol. 81：826- 835，2009. (C)2009 Wiley-Liss，Inc.
Occult HBV infection is defined as the persistence of HBV DNA in individuals negative for HBV surface antigen (HBsAg), and many different mechanisms have been reported in different countries. However, in China, one of the endemic areas for HBV infection, no reports have been published on occult HBV infection. The present study investigated the virological features and the mechanism of occult HBV infection in China. Full-length HBV DNA from eight patients with occult HBV infection (S1-S8) and three HBsAg-positive cases (SWT1-SWT3) was cloned and sequenced. Additionally, four entire linear HBV genomes from occult cases were transfected transiently into HepG2 cells. The sequencing results showed two major mutations in patients with occult HBV infection as follows: deletions in the pre-S1 (S3, S4, and S7) and X (S1, S2, and S5) regions. Such deletions covered the S promoter and the basal core promoter (BCP), and function analysis of these variants also showed a decrease in DNA replication and antigen expression. Two patients with occult infection (S6 and S8) had no mutations capable of interfering with viral replication and gene expression in the major viral population. Thus, the deletions in the S promoter and the BCP regions that disable the regulatory elements may be the reason for the absence of HBsAg, and multiple mechanisms may be responsible for occult HBV infection. J. Med. Virol. 81:826-835,2009. (C) 2009 Wiley-Liss, Inc.