乙型肝炎病毒：具有多个面孔和显着复制策略的古老病毒的

StephenW

Antiviral Res. 2018 Jul 27. pii: S0166-3542(17)30816-1. doi: 10.1016/j.antiviral.2018.07.019. [Epub ahead of print]
Hepatitis B virus: The challenge of an ancient virus with multiple faces and a remarkable replication strategy.
Caballero A1, Tabernero D2, Buti M3, Rodríguez-Frías F4.
Author information

1
    Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona (UAB), 119-129 Passeig Vall, d'Hebron, Clinical Laboratories, 08035 Barcelona, Spain. Electronic address: [email protected].
2
    Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona (UAB), 119-129 Passeig Vall, d'Hebron, Clinical Laboratories, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 3-5 Avenida Monforte de Lemos, pavilion 11, 28029 Madrid, Spain. Electronic address: [email protected].
3
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 3-5 Avenida Monforte de Lemos, pavilion 11, 28029 Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona (UAB), 119-129 Passeig Vall d'Hebron, General Hospital, Internal Medicine 2, 08035 Barcelona, Spain. Electronic address: [email protected].
4
    Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona (UAB), 119-129 Passeig Vall, d'Hebron, Clinical Laboratories, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 3-5 Avenida Monforte de Lemos, pavilion 11, 28029 Madrid, Spain. Electronic address: [email protected].

Abstract

The hepatitis B virus (HBV) is the prototype member of the Hepadnaviridae, an ancient family of hepatotropic DNA viruses, which may have originated from 360 to 430 million years ago and with evidence of endogenization in reptilian genomes >200 million years ago. The virus is currently estimated to infect more than 250 million humans. The extremely successful spread of this pathogen among the human population is explained by its multiple particulate forms, effective transmission strategies (particularly perinatal transmission), long induction period and low associated mortality. These characteristics confer selective advantages, enabling the virus to persist in small, disperse populations and spread worldwide, with high prevalence rates in many countries. The HBV replication strategy is remarkably complex and includes a multiplicity of particulate structures. In addition to the common virions containing DNA in a relaxed circular (rcDNA) or double-stranded linear (dslDNA) forms, the viral population includes virion-like particles containing RNA or "empty" (viral envelopes and capsids without genomes), subviral particles (only an envelope) and even naked capsids. Consequently, several forms of the genome coexist in a single infection: (i) the "traveler" forms found in serum, including rcDNA and dslDNA, which originate from retrotranscription of a messenger RNA (the pregenomic RNA, another form of the viral genome itself) and (ii) forms confined to the host cell nucleus, including covalently closed circular DNA (cccDNA), which leads to a minichromosome form associated with histones and viral proteins, and double-stranded DNA integrated into the host genome. This complex composition lends HBV a kind of "multiple personality". Are these additional particles and genomic forms simple intermediaries/artifacts or do they play a role in the viral life cycle?
KEYWORDS:

Chronic hepatitis B; Hepadnaviridae; Hepatitis B virus; Vertical transmission; Viral life cycle

PMID:
    30059722
DOI:
    10.1016/j.antiviral.2018.07.019

StephenW

抗病毒药物2018年7月27日.pii：S0166-3542（17）30816-1。 doi：10.1016 / j.antiviral.2018.07.019。 [提前打印]
乙型肝炎病毒：具有多个面孔和显着复制策略的古老病毒的挑战。
Caballero A1，Tabernero D2，Buti M3，Rodríguez-FríasF4。
作者信息

1
    肝脏病理学部，生物化学和微生物学系，巴勒斯坦大学医学院和巴塞罗那自治大学（UAB），119-129 Passeig Vall，d'Hebron，临床实验室，08035巴塞罗那，西班牙。电子地址：[email protected]。
2
    肝脏病理科，巴勒斯坦大学医学院和巴塞罗那自治大学（UAB）生物化学与微生物学系，119-129 Passeig Vall，d'Hebron，临床实验室，08035巴塞罗那，西班牙; CentrodeInvestigaciónBiomédicaenRed deEnfermedadesHepáticasyDigestivas（CIBERehd），Instituto de Salud Carlos III，3-5 Avenida Monforte de Lemos，Pavilion 11,28029 Madrid，Spain。电子地址：[email protected]。
3
    CentrodeInvestigaciónBiomédicaenRed deEnfermedadesHepéticasyDigestivas（CIBERehd），Instituto de Salud Carlos III，3-5 Avenida Monforte de Lemos，Pavilion 11,28029 Madrid，Spain;肝脏科，巴勒斯坦大学医院内科和巴塞罗那自治大学（UAB），119-129 Passeig Vall d'Hebron，General Hospital，Internal Medicine 2,08035 Barcelona，Spain。电子地址：[email protected]。
4
    肝脏病理科，巴勒斯坦大学医学院和巴塞罗那自治大学（UAB）生物化学与微生物学系，119-129 Passeig Vall，d'Hebron，临床实验室，08035巴塞罗那，西班牙; CentrodeInvestigaciónBiomédicaenRed deEnfermedadesHepáticasyDigestivas（CIBERehd），Instituto de Salud Carlos III，3-5 Avenida Monforte de Lemos，Pavilion 11,28029 Madrid，Spain。电子地址：[email protected]。

抽象

乙型肝炎病毒（HBV）是Hepadnaviridae的原型成员，Hepadnaviridae是一个古老的嗜肝DNA病毒家族，可能起源于360至4.3亿年前，并且有证据表明在2亿年前的爬行动物基因组中内源化。目前估计该病毒感染超过2.5亿人。这种病原体在人群中的极其成功的传播可以通过其多种微粒形式，有效的传播策略（特别是围产期传播），长诱导期和低相关死亡率来解释。这些特征赋予选择性优势，使病毒能够在小的，分散的群体中持续存在并在全世界传播，在许多国家具有高流行率。 HBV复制策略非常复杂，包括多种颗粒结构。除了含有松弛环状（rcDNA）或双链线性（dslDNA）形式的DNA的常见病毒颗粒外，病毒群还包括含有RNA或“空”（病毒包膜和无基因组的衣壳）的病毒颗粒，亚病毒颗粒（只有一个信封）甚至是裸露的衣壳。因此，几种形式的基因组在单一感染中共存：（i）血清中发现的“旅行者”形式，包括rcDNA和dslDNA，其源自信使RNA的逆转录（前基因组RNA，病毒基因组本身的另一种形式） ）和（ii）局限于宿主细胞核的形式，包括共价闭合环状DNA（cccDNA），其导致与组蛋白和病毒蛋白相关的微染色体形式，以及整合到宿主基因组中的双链DNA。这种复杂的成分为HBV带来了一种“多重人格”。这些额外的颗粒和基因组形式是简单的中间体/文物还是它们在病毒生命周期中起作用？
关键词：

慢性乙型肝炎;嗜肝;乙型肝炎病毒;垂直传输;病毒生命周期

结论：
    30059722
DOI：
    10.1016 / j.antiviral.2018.07.019