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乙型肝炎病毒的分子生物学及X基因的作用

Molecular biology of the hepatitis B virus and role of the X gene.

作者信息

Wei Y, Neuveut C, Tiollais P, Buendia M-A

机构信息

Unité oncogenèse et virologie moléculaire, département de virologie, Institut Pasteur, 28, rue du Dr-Roux, 75724 Paris cedex 15, France.

出版信息

Pathol Biol (Paris). 2010 Aug;58(4):267-72. doi: 10.1016/j.patbio.2010.03.005. Epub 2010 May 18.

DOI:10.1016/j.patbio.2010.03.005
PMID:20483545
Abstract

The hepatitis B virus (HBV) is a widespread human pathogen and a major health problem in many countries. Molecular cloning and sequencing of the viral DNA genome has demonstrated a small and compact structure organized into four overlapping reading frames that encode the viral proteins. Besides structural proteins of the core and the envelope, HBV encodes a DNA polymerase with reverse transcriptase activity, a secreted antigen of unknown function, and a transcriptional activator that is essential for viral replication. Major steps of the viral life cycle have been unraveled, including transcription of all viral RNAs from nuclear covalently closed circular DNA (cccDNA), followed by encapsidation of pregenomic RNA, a more-than-genome length transcript, and reverse transcription of pregenomic RNA leading to asymmetric synthesis of the DNA strands. Although HBV has been recognized as a human tumor virus, no direct transforming activity could be evidenced in different cellular and animal models. However, the transcriptional regulatory protein HBx encoded by the X gene is endowed with weak oncogenic activity. HBx harbors pleiotropic activities and plays a major role in HBV pathogenesis and in liver carcinogenesis.

摘要

乙型肝炎病毒(HBV)是一种广泛传播的人类病原体,在许多国家都是一个主要的健康问题。病毒DNA基因组的分子克隆和测序表明,其结构小而紧凑,由四个重叠的阅读框组成,这些阅读框编码病毒蛋白。除了核心蛋白和包膜蛋白外,HBV还编码一种具有逆转录酶活性的DNA聚合酶、一种功能未知的分泌抗原以及一种对病毒复制至关重要的转录激活因子。病毒生命周期的主要步骤已被阐明,包括从核共价闭合环状DNA(cccDNA)转录所有病毒RNA,随后将前基因组RNA(一种长度超过基因组的转录本)包装起来,并对前基因组RNA进行逆转录,导致DNA链的不对称合成。尽管HBV已被公认为一种人类肿瘤病毒,但在不同的细胞和动物模型中均未证实其具有直接转化活性。然而,由X基因编码的转录调节蛋白HBx具有微弱的致癌活性。HBx具有多效性活动,在HBV发病机制和肝癌发生中起主要作用。

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