Gastroenterology

Gastroenterology

Volume 156, Issue 2, January 2019, Pages 384-399
Gastroenterology

Review
Insights From Deep Sequencing of the HBV Genome—Unique, Tiny, and Misunderstood

https://doi.org/10.1053/j.gastro.2018.07.058Get rights and content
Under a Creative Commons license
open access

Hepatitis B virus (HBV) is a unique, tiny, partially double-stranded, reverse-transcribing DNA virus with proteins encoded by multiple overlapping reading frames. The substitution rate is surprisingly high for a DNA virus, but lower than that of other reverse transcribing organisms. More than 260 million people worldwide have chronic HBV infection, which causes 0.8 million deaths a year. Because of the high burden of disease, international health agencies have set the goal of eliminating HBV infection by 2030. Nonetheless, the intriguing HBV genome has not been well characterized. We summarize data on the HBV genome structure and replication cycle, explain and quantify diversity within and among infected individuals, and discuss advances that can be offered by application of next-generation sequencing technology. In-depth HBV genome analyses could increase our understanding of disease pathogenesis and allow us to better predict patient outcomes, optimize treatment, and develop new therapeutics.

Keywords

Hepatitis B Virus
Genotype
Diversity
Evolution

Abbreviations used in the paper

cccDNA
covalently closed circular DNA
dsDNA
double-stranded DNA
HBsAg
hepatitis B surface antigen
HBeAg
hepatitis B e antigen
HBV
hepatitis B virus
HCC
hepatocellular carcinoma
HIV
human immunodeficiency virus
NGS
next-generation sequencing
ORF
open reading frame
P
reverse transcriptase polymerase
RC-DNA
relaxed circular DNA
RT
reverse transcriptase
S
surface

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Conflicts of interest Peter Revill has received research funding from Gilead Sciences. Philippa C. Matthews has a consultancy role in Immunocore and is on the Editorial Board of BMC Infectious Diseases.

Funding Philippa C. Matthews is funded by a Wellcome Trust Intermediate Fellowship (grant 110110). Peter Revill’s research program is funded in part by the NHMRC (APP1159305). Jane A. McKeating is funded by the EU 2020 Research and Innovation Programme (grant agreement 667273 Hep-CAR consortia) and the Wellcome Trust (IA 200838/Z/16/Z).