Molecular Biology of the Hepatitis B Virus for Clinicians
Molecular Biology of the Hepatitis B Virus for Clinicians
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DOI：
10.1016/j.jceh.2012.10.003
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发表时间：
2012-12-01
影响因子：
3
通讯作者：
Chakravarty, Runu
中科院分区：
文献类型：
--
作者：
Datta, Sibnarayan;Chatterjee, Soumya;Chakravarty, Runu
乙肝病毒感染是全球主要的健康问题之一，特别是在经济欠发达或发展中国家。乙肝病毒感染可导致许多临床后果，包括慢性感染、肝硬变和肝癌。它是十大死因之一，每年造成约100万人死亡。尽管已经有了高效的疫苗和有效的抗病毒药物，但乙肝病毒感染仍然是一个重要的临床问题，特别是在那些由于经济原因无法为大量人口接种疫苗的高流行地区。尽管就病毒粒子和基因组大小而言，乙肝病毒是最小的病毒之一，但它有许多独特的特征，使其完全不同于其他DNA病毒。它具有部分双链DNA，具有高度复杂的基因组组织、生活史和自然历史。与其他DNA病毒显著不同的是，它使用一种名为前基因组RNA(PgRNA)的RNA中间体和逆转录酶进行基因组复制。基因组复制是通过在基因组中编码的直接重复序列促进的复杂的引物转移机制来完成的。此外，基因组已经进化到这样一种方式，基因组的每个单核苷酸要么用于编码病毒蛋白，要么用作调节区，或者两者兼而有之。此外，它利用内部框内翻译起始密码子，以及来自同一RNA的不同阅读框架来产生具有不同功能的不同蛋白质。乙肝病毒也表现出相当大的遗传变异，这与临床结果、复制潜力、治疗反应等有关。本文旨在从分子角度综述病毒生命周期的基本事件，包括病毒复制、转录和翻译，并强调乙肝病毒遗传变异的临床意义。
Hepatitis B virus (HBV) infection is one of the major global health problems, especially in economically underdeveloped or developing countries. HBV infection can lead to a number of clinical outcomes including chronic infection, cirrhosis and liver cancer. It ranks among the top 10 causes of death, being responsible for around 1 million deaths every year. Despite the availability of a highly efficient vaccine and potent antiviral agents, HBV infection still remains a significant clinical problem, particularly in those high endemicity areas where vaccination of large populations has not been possible due to economic reasons.Although HBV is among the smallest viruses in terms of virion and genome size, it has numerous unique features that make it completely distinct from other DNA viruses. It has a partially double stranded DNA with highly complex genome organization, life cycle and natural history. Remarkably distinct from other DNA viruses, it uses an RNA intermediate called pregenomic RNA (pgRNA) and reverse transcriptase for its genome replication. Genome replication is accomplished by a complex mechanism of primer shifting facilitated by direct repeat sequences encoded in the genome. Further, the genome has evolved in such a manner that every single nucleotide of the genome is used for either coding viral proteins or used as regulatory regions or both. Moreover, it utilizes internal in-frame translation initiation codons, as well as different reading frames from the same RNA to generate different proteins with diverse functions. HBV also shows considerable genetic variability which has been related with clinical outcomes, replication potential, therapeutic response etc. This review aims at reviewing fundamental events of the viral life cycle including viral replication, transcription and translation, from the molecular standpoint, as well as, highlights the clinical relevance of genetic variability of HBV.