Hepatitis B virus molecular biology and pathogenesis.
Hepatitis B virus molecular biology and pathogenesis.
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DOI：
10.20517/2394-5079.2016.05
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Bouchard MJ
中科院分区：
文献类型：
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作者：
Lamontagne RJ;Bagga S;Bouchard MJ
作为专性细胞内寄生物，病毒需要宿主细胞提供有利于病毒复制的环境。因此，病毒经常采用破坏宿主细胞信号传导过程的机制。虽然对病毒复制周期有益，但病毒诱导的宿主细胞信号传导过程的失调可能对宿主细胞生理学有害，并可能导致病毒相关的发病机制，包括对于致癌病毒，细胞转化和癌症进展。这些致癌病毒中包括B型肝炎病毒（HBV）。尽管HBV疫苗是可用的，但全世界仍有3.5 - 5亿人慢性感染HBV，并且这些慢性感染个体中的相当数量将发展成肝细胞癌（HCC）。流行病学研究表明，慢性HBV感染是HCC发生的主要危险因素。在全球范围内，HCC是癌症相关死亡的第二大原因，强调需要了解调节HBV复制和HBV相关HCC发展的机制。HBV是嗜肝DNA病毒科的原型成员;该病毒家族的成员具有狭窄的宿主范围，并且主要感染其各自宿主中的肝细胞。嗜肝DNA病毒的基因组非常小和紧凑，开放阅读框的独特排列，以及利用RNA中间体的逆转录产生DNA基因组的复制策略是嗜肝DNA病毒科的区别特征。在这篇综述中，我们提供了HBV生物学的全面描述，总结了用于研究HBV感染的模型系统，并强调了将慢性HBV感染与HCC发展联系起来的潜在机制。例如，HBV X蛋白（HBx），一种对HBV复制很重要的关键调节性HBV蛋白，被认为在HBV诱导的HCC的发展中起辅助因子作用，我们强调了HBx可能有助于HBV相关HCC发展的功能。
As obligate intracellular parasites, viruses need a host cell to provide a milieu favorable to viral replication. Consequently, viruses often adopt mechanisms to subvert host cellular signaling processes. While beneficial for the viral replication cycle, virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead to virus-associated pathogenesis, including, for oncogenic viruses, cell transformation and cancer progression. Included among these oncogenic viruses is the hepatitis B virus (HBV). Despite the availability of an HBV vaccine, 350–500 million people worldwide are chronically infected with HBV, and a significant number of these chronically infected individuals will develop hepatocellular carcinoma (HCC). Epidemiological studies indicate that chronic infection with HBV is the leading risk factor for the development of HCC. Globally, HCC is the second highest cause of cancer-associated deaths, underscoring the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC. HBV is the prototype member of the Hepadnaviridae family; members of this family of viruses have a narrow host range and predominately infect hepatocytes in their respective hosts. The extremely small and compact hepadnaviral genome, the unique arrangement of open reading frames, and a replication strategy utilizing reverse transcription of an RNA intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae. In this review, we provide a comprehensive description of HBV biology, summarize the model systems used for studying HBV infections, and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC. For example, the HBV X protein (HBx), a key regulatory HBV protein that is important for HBV replication, is thought to play a cofactor role in the development of HBV-induced HCC, and we highlight the functions of HBx that may contribute to the development of HBV-associated HCC.