乙型肝炎病毒聚合酶

StephenW

乙型肝炎病毒聚合酶
Daniel N Clark 1、Razia Tajwar 2、Jianming Hu 3、John E Tavis 4
隶属关系
隶属关系

    1
    美国犹他州奥格登韦伯州立大学微生物学系。
    2
    美国密苏里州圣路易斯圣路易斯大学医学院分子微生物学和免疫学系。
    3
    宾夕法尼亚州立大学医学院微生物学和免疫学系，美国宾夕法尼亚州赫尔希。
    4
    美国密苏里州圣路易斯圣路易斯大学医学院分子微生物学和免疫学系。电子地址：[email protected]。

    PMID：34861937 DOI：10.1016/bs.enz.2021.06.010

抽象的

乙型肝炎病毒 (HBV) 是一种嗜肝、部分双链 DNA 病毒，通过逆转录复制，是慢性肝病和肝细胞癌的主要原因。逆转录由具有蛋白质引发、RNA 和 DNA 依赖性 DNA 合成（即逆转录酶）和核糖核酸酶 H 活性的四结构域多功能 HBV 聚合酶 (P) 蛋白催化。 P 也可能促进逆转录过程中发生的三链转移，它可能参与 HBV 的免疫逃避。逆转录由 P 氨基末端结构域中的酪氨酸残基引发，并且 P 在整个逆转录过程中保持共价连接到产物 DNA 上。 P 的逆转录酶活性是主导 HBV 治疗的核苷（酸）类似物药物的目标，而 P 是开发针对逆转录酶和核糖核酸酶 H 活性的新药物的持续努力的目标。尽管 P 催化了不寻常的逆转录途径以及 P 对 HBV 治疗的重要性，但由于研究酶的大量技术挑战，对 HBV P 的酶学和结构的了解严重滞后于逆转录病毒逆转录酶。更好地了解 P 将拓宽我们对自然界中逆转录元素多样性的认识，并将有助于改善对慢性 HBV 感染者的治疗。

关键词：酶学；乙型肝炎病毒;聚合酶；蛋白质引发；逆转录；核糖核酸酶 H。

版权所有 © 2021 Elsevier Inc。保留所有权利。

StephenW

The hepatitis B virus polymerase
Daniel N Clark  1 , Razia Tajwar  2 , Jianming Hu  3 , John E Tavis  4
Affiliations
Affiliations

    1
    Department of Microbiology, Weber State University, Ogden, UT, United States.
    2
    Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, United States.
    3
    Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, United States.
    4
    Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, United States. Electronic address: [email protected].

    PMID: 34861937 DOI: 10.1016/bs.enz.2021.06.010

Abstract

Hepatitis B virus (HBV) is a hepatotropic, partially double-stranded DNA virus that replicates by reverse transcription and is a major cause of chronic liver disease and hepatocellular carcinoma. Reverse transcription is catalyzed by the four-domain multifunctional HBV polymerase (P) protein that has protein-priming, RNA- and DNA-dependent DNA synthesis (i.e., reverse transcriptase), and ribonuclease H activities. P also likely promotes the three strand transfers that occur during reverse transcription, and it may participate in immune evasion by HBV. Reverse transcription is primed by a tyrosine residue in the amino-terminal domain of P, and P remains covalently attached to the product DNA throughout reverse transcription. The reverse transcriptase activity of P is the target for the nucleos(t)ide analog drugs that dominate HBV treatment, and P is the target of ongoing efforts to develop new drugs against both the reverse transcriptase and ribonuclease H activities. Despite the unusual reverse transcription pathway catalyzed by P and the importance of P to HBV therapy, understanding the enzymology and structure of HBV P severely lags that of the retroviral reverse transcriptases due to substantial technical challenges to studying the enzyme. Obtaining a better understanding of P will broaden our appreciation of the diversity among reverse transcribing elements in nature, and will help improve treatment for people chronically infected with HBV.

Keywords: Enzymology; Hepatitis B virus; Polymerase; Protein-priming; Reverse transcription; Ribonuclease H.

Copyright © 2021 Elsevier Inc. All rights reserved.