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Hepatitis B Virus and Liver Disease pp 1–27Cite as

Molecular Virology and Life Cycle of Hepatitis B Virus

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Abstract

Hepatitis B virus (HBV) is the prototypic member of Orthohepadnaviridae, hepadnaviruses that can lead to transient or persistent infection. When left untreated, chronic HBV infection leads to severe liver damage culminating in hepatocellular carcinoma (HCC). HCC represents the third cause of cancer-related death worldwide with more than 800,000 deaths every year, thus constituting a major health issue.

HBV genomic DNA is a relaxed-circular partially double-stranded DNA (rcDNA), which has to be converted into a covalently closed circular DNA (cccDNA) in hepatocytes nucleus to allow viral replication. cccDNA represents the viral genomic reservoir and the template for viral transcription of the viral pregenomic RNA (pgRNA) intermediate, which is then reverse-transcribed back to viral DNA. The persistence of cccDNA in infected hepatocytes accounts for chronicity of infection and the low rate of cure. Here, we review the current body of knowledge on HBV biology, with a particular focus on the complex jigsaw puzzle of HBV molecular mechanisms of replication.

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Abbreviations

5’ RACE:

5’ Rapid amplification cDNA end

AGL:

Antigenic loop

AP-1:

Activator protein-1

BCP:

Basic core promoter

C/EBP:

CCAAT/enhancer-binding proteins

cccDNA:

Covalently closed circular DNA

CHB:

Chronic hepatitis B

CTD:

Carboxy terminal domain

Cul4:

Cullin 4

DDB1:

DNA damage-binding protein 1

DNA:

Deoxyribonucleic acid

DNMT:

DNA methyltransferase

DR1/2:

Direct repeat 1/2

dsl-DNA:

Double-stranded linear DNA

DynLL1:

Dynein light chain 1

EnhI/II:

Enhancer I/II

ESCRT:

Export and sorting complex required for transport

FEN1:

Flap endonuclease 1

FXR:

Farnesoid X receptor

H 2a/2b/3/4:

Histone 2a/2b/3/4

HAT:

Histone acetyl transferase

HBDSP:

Hepatitis B double spliced protein

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B s antigen

HBSP:

Hepatitis B spliced protein

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HDAC:

Histone deacetylase

HGS/HRS:

Hepatocyte growth factor-regulated tyrosine kinase substrate

HNF:

Hepatocyte nuclear factor

HSPG:

Heparan sulfate proteoglycan

kb:

Kilobase

kDa:

Kilodalton

m6A:

N6 methyladenosine

METTL3/14:

Methyltransferase-Like 3/14

miRNA:

MicroRNA

mRNA:

Messenger RNA

MVB:

Multivesicular bodies

NES:

Nuclear export signal

NF1:

Nuclear factor 1

NF-κB:

Nuclear factor-κ B

NPC:

Nuclear pore complex

nt:

Nucleotide

NTCP:

Na+-taurocholate cotransporting polypeptide

NUC:

Nucleos(t)ide analog

Nup153:

Nucleoporin 153

ORF:

Open riding frame

PAPD5/7:

PolyA-RNA polymerase-associated domain containing protein 5/7

PAS:

Polyadenylation signal

PCNA:

Proliferating cell nuclear antigen

pgRNA:

Pregenomic RNA

Pol:

Polymerase

PolyA:

Polyadenylation

PRE:

Posttranscriptional regulatory element

P-S FP:

Polymerase-surface fusion protein

PSF:

PTB-associated splicing factor

PTM:

Posttranslational modification

Rab5/7:

Ras-Associated protein 5/7

rcDNA:

Relaxed circular DNA

RER:

Rough endoplasmic reticulum

RNA:

Ribonucleic acid

Smc5/6:

Structural maintenance of chromosomes 5/6

SP1:

Singly spliced product 1

SRE:

Splicing regulatory element

SVP:

Subviral particle

TBP:

TATA-binding protein

TDP2:

Tyrosyl-DNA phosphodiesterase 2

TP:

Terminal protein

TREX:

Transcription and export factor

TSS:

Transcription start site

URR:

Upper regulatory region

WHV:

Woodchuck hepatitis virus

YTHDF:

YTH domain-containing family protein

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Authors and Affiliations

  1. UMR INSERM 1052 - CNRS 5286, Cancer Research Center of Lyon (CRCL), Lyon Cedex 03, France

    Fleur Chapus, Maria Guadalupe Martinez, Barbara Testoni & Fabien Zoulim

  2. Department of Hepatology, Hospices Civils de Lyon, Croix Rousse Hospital, Lyon, France

    Fabien Zoulim

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  1. Fleur Chapus
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  2. Maria Guadalupe Martinez
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  3. Barbara Testoni
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  4. Fabien Zoulim
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Correspondence to Fabien Zoulim .

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  1. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

    Jia-Horng Kao

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Chapus, F., Martinez, M.G., Testoni, B., Zoulim, F. (2021). Molecular Virology and Life Cycle of Hepatitis B Virus. In: Kao, JH. (eds) Hepatitis B Virus and Liver Disease. Springer, Singapore. https://doi.org/10.1007/978-981-16-3615-8_1

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