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Hepatitis B Virus Virology and Replication

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Hepatitis B Virus in Human Diseases

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

Hepatitis B virus (HBV) is an enveloped virus with an internal icosahedral nucleocapsid (NC) enclosing a partially double-stranded, relaxed circular DNA (rcDNA) genome, which is replicated through reverse transcription of a RNA intermediate, the pregenomic RNA (pgRNA). The virus specifically infects human hepatocytes by binding the cell surface receptor, sodium taurocholate cotransporting polypeptide, which was only recently identified. Upon cell entry, HBV is believed to deliver its internal NC to the nuclear pore complex where rcDNA is released into the nucleus. rcDNA is then converted, in an ill-understood process, to a covalently closed circular DNA (cccDNA), which serves as the transcriptional template for the production of all viral RNAs, subject to regulation by epigenetic mechanisms as well as ubiquitous and liver-enriched transcriptional factors. Upon translation, the viral reverse transcriptase assembles with pgRNA, with the help of host factors, into a ribonucleoprotein complex, which triggers initiation of viral reverse transcription using a novel protein priming mechanism as well as the assembly of immature progeny NCs with the viral capsid protein. Reverse transcription within NCs then converts pgRNA into the mature rcDNA, which can be recycled back to the nucleus for conversion to more cccDNA, or secreted in progeny virions extracellularly with the viral envelope proteins, completing the life cycle. The only target in this life cycle that has been exploited successfully so far for antiviral therapy is the DNA synthesis activity of the viral reverse transcriptase, but others are being actively explored. HBV replication also leads to the secretion of a large excess of subviral particles and a soluble antigen, which are nonessential for the virus but have greatly contributed, and will continue to contribute, to the diagnosis and prevention of HBV infections.

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Abbreviations

C:

Core

cccDNA:

Covalently closed circular DNA

CDK:

Cyclin-dependent protein kinase

CTD:

C-Terminal domain

DHBV:

Duck hepatitis B virus

dp:

Deproteinated

DR:

Direct repeat

DS:

Double-stranded

dslDNA:

Double-stranded linear DNA

EM:

Electron microscopy

ER:

Endoplasmic reticulum

HBcAg:

Hepatitis B core antigen

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HBx:

Hepatitis B X protein

HNF:

Hepatocyte nuclear factor

HSP:

Heat shock protein

L:

Large envelope protein

M:

Middle envelope protein

NC:

Nucleocapsid

NLS:

Nuclear localization signal

nt:

Nucleotide

NTCP:

Sodium taurocholate cotransporting polypeptide

NTD:

N-Terminal domain

ORF:

Open reading frame

P:

Polymerase

PF:

Protein-free

pgRNA:

Pregenomic RNA

PKC:

Protein kinase C

PreC:

Precore

rcDNA:

Relaxed circular DNA

RNP:

Ribonucleoprotein

RT:

Reverse transcriptase

S:

Small envelope protein

SRPK:

Serine-arginine protein kinase

SS:

Single-stranded

TP:

Terminal protein

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Acknowledgement

I thank colleagues in my laboratory for critical reading of the manuscript and helpful comments. I acknowledge support by the National Institutes of Health, the American Cancer Society, the American Liver Foundation, and the Medical Foundation for work carried out in my laboratory.

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  1. Department of Microbiology and Immunology-H107, The Penn State University College of Medicine, 500 University Dr., Hershey, PA, 17033, USA

    Jianming Hu M.D., Ph.D.

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  1. Jianming Hu M.D., Ph.D.
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Correspondence to Jianming Hu M.D., Ph.D. .

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  1. Chang Gung University, Chang Gung Memorial Hospital, Taipei, Taiwan

    Yun-Fan Liaw

  2. INSERM Unit 1052, Hospices Civils de Lyon, Lyon University, Lyon, France

    Fabien Zoulim

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Hu, J. (2016). Hepatitis B Virus Virology and Replication. In: Liaw, YF., Zoulim, F. (eds) Hepatitis B Virus in Human Diseases. Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-22330-8_1

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  • DOI: https://doi.org/10.1007/978-3-319-22330-8_1

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