Trends in Microbiology | Microbe of The Month

Special Issue: Broad Concepts in Microbiology

Hepatitis B Virus
Chiaho Shih,1,2,3,* Ching-Chun Yang,1,2 Gansukh Choijilsuren,1,2 Chih-Hsu Chang,1,3 and An-Ting Liou1
1
Institute of Biomedical Sciences (IBMS), Academia Sinica, Taipei, Taiwan
2
Taiwan International Graduate Program (TIGP) in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan
3
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan

KEY FACTS:
Virion
HBs subviral parƟcles No known reservoir. HBV has a tight
Heparan species barrier.
sulfate Na+ bile acid
proteoglycan symporter Discovered by Dr Baruch Blumberg in
Entry 1967 (Nobel Laureate in 1976).
Hepatocyte Viral particles are infectious, enveloped
spherical virions (42 nm); there are
MulƟvesicular excessive numbers of noninfectious
Golgi body
HBs subviral particles (22 nm), and
ER icosahedral nucleocapsids (27–32 nm).

rcDNA Morphogenesis The HBV genome is 3.2 kb DNA;

partially double-stranded rc DNA
occurs in virions, and ccc DNA occurs
rcDNA
in the nucleus of infected hepatocytes.
rcDNA
Viral antigens include core (HBc),
TranslaƟon ssDNA surface (HBs, Australia Ag), polymerase
cccDNA of HBsAg
(pol contains a reverse transcriptase
A(n) A(n) domain), and HBx.
A(n)

A(n) A(n)
TranscripƟon A(n) A(n) TranslaƟon & pgRNA HBV animal models include the
capsid assembly chimpanzee, bat, woodchuck, ground
squirrel, and duck.

DISEASE FACTS:
Hepatitis B virus (HBV) is a common worldwide blood-borne pathogen. Chronic hepatitis B can progress to an Transmission is blood-borne or through
inactive carrier state, and then, in some patients, give rise to cirrhosis and cancer of the liver, leading to death. body fluids; HBV can be transmitted
An HBV surface-antigen vaccine is effective, but treatments are currently not curative. HBV replicates via reverse perinatally (mother-to-infant) or
transcription. Its covalently closed circular (ccc) DNA in the nucleus encodes a pregenomic RNA (pgRNA), which can horizontally through close contacts.
be encapsidated by HBV polymerase. Reverse transcription occurs in the capsids by using the pgRNA as a template
Diagnosis relies on ELISA of serum
for the synthesis of single-stranded linear and then partially double-stranded relaxed circular (rc) DNA. Capsids
HBs, HBe, anti-HBs, and anti-HBc, or
containing a mature rc DNA genome target to the nucleus for ccc DNA synthesis. Persistent HBV infection is caused
by PCR for serum HBV DNA.
mainly by ccc DNA and immune tolerance to HBV antigens in the liver. Unlike acute infection, chronic carriers contain
only a low level of HBV core-antigen-specific T cell activity, contributing to the lack of viral clearance. Coinfection occurs less frequently with
HIV, hepatitis C virus, or hepatitis D virus.
TAXONOMY AND CLASSIFICATION: During chronic infection, HBs persists
Immune Immune InacƟve ORDER: Unassigned
tolerance clearance carrier for longer than 6 months.
FAMILY: Hepadnaviridae
GENUS: Orthohepadnavirus HBV can cause a wide range of
HBsAg α-HBs SPECIES: Hepatitis B virus diseases, including subclinical, acute,
Double-stranded DNA virus and chronic hepatitis as well as
HBeAg α-HBe
fibrosis, cirrhosis, hepatocellular
carcinoma, and liver failure.
HBV DNA
Alanine
aminotransferase/ Hepatitis B vaccine is safe and effective
aspartate (95% efficacy). It was the first human
Liver
aminotransferase
inflammaƟon cancer vaccine and the first
recombinant vaccine.
HBV can be treated with nucleos(t)ide
10 20 30 40 50 ≥ 60 analogs and (PEG)-interferon-
HBV exposure (years) a  ribavirin.

*Correspondence:
cshih@ibms.sinica.edu.tw (C. Shih).

386 Trends in Microbiology, April 2018, Vol. 26, No. 4 © 2018 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.tim.2018.01.009
Trends in Microbiology | Microbe of The Month
Resources
www.who.int/mediacentre/factsheets/fs204/en/
www.hepb.org/treatment-and-management/drug-watch/

Literature
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3. Beasley, R.P. et al. (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet 2, 1129–1133

4. Chang, M.H. (1997) Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group.
N. Engl. J. Med. 336, 1855–1859

5. Galibert, F. et al. (1979) Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature 281, 646–650

6. Guidotti, L.G. et al. (1999) Viral clearance without destruction of infected cells during acute HBV infection. Science 284, 825–829

7. Summers, J. and Mason, W.S. (1982) Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate. Cell 29, 403–415

8. Sureau, C. et al. (1986) Production of hepatitis B virus by a differentiated human hepatoma cell line after transfection with cloned circular HBV DNA. Cell 47, 37–47

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10. Yan, H. et al. (2012) Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife 1, e00049

Trends in Microbiology, April 2018, Vol. 26, No. 4 © 2018 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.tim.2018.01.009 387