Molecular Virology and Life Cycle
The hepatitis B virus is a prevalent human infection with no cure at present. It is a significant cause of global morbidity and mortality and has achieved its persistence in humans via its complex life cycle and ability to use its few protein products in
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Molecular Virology and Life Cycle Darren J. Wong and Stephen A. Locarnini
Abstract
The hepatitis B virus is a prevalent human infection with no cure at present. It is a significant cause of global morbidity and mortality and has achieved its persistence in humans via its complex life cycle and ability to use its few protein products in a multifunctional manner to subvert and evade immune detection and clearance. These aspects of the virus are discussed in detail, as are the development of clinically important mutations in the viral genome that develop as a result of host immune selection, as well as those selected by the introduction of antiviral therapy or vaccination. Keywords
Hepatitis B • Molecular Virology • Lifecycle • Antiviral Resistance
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Classification
The hepatitis B virus (HBV) is the most well-known member of the virus family Hepadnaviridae. The species in this family are split amongst two genera— Avihepadnavirus and Orthohepadnavirus—with human HBV belonging to the latter. HBV has been further classified into ten genotypes, A to J, which are based D.J. Wong Department of Gastroenterology, St. Vincent’s Hospital, Melbourne, Fitzroy, VIC 3065, Australia e-mail: [email protected] S.A. Locarnini (*) Department of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC 3000, Australia e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2018 J.-H. Kao, D.-S. Chen (eds.), Hepatitis B Virus and Liver Disease, https://doi.org/10.1007/978-981-10-4843-2_1
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D.J. Wong and S.A. Locarnini
on whole-genome nucleotide diversity of at least 8% (Norder et al. 1994; Stuyver et al. 2000; Kann and Gerlich 2005; Tatematsu et al. 2009; Olinger et al. 2008). There is distinct geographical variation amongst these genotypes (Table 1.1). Table 1.1 Overview of the ten genotypes of HBV. Adapted from Locarnini et al. (2013). Note that genotype J has yet to be verified, as only one case has been isolated Genome length (nt) 3221
Frequency of mutationa PC BCP Uncommon Common
3215
Common
Uncommon
3215
Common
Common
3182
Common
Common
3212
NK
NK
3215
Uncommon
NK
G
3248
Very common
NK
H
3215
NK
NK
I J
3215 3182
– –
– –
Genotype A
Subtype A1 A2
B
B1 B2 B3 B4 C1 C2 C3 C4
C
D
C5 D1 D2 D3 D4
E F
F1 F2 F3 F4
Global distribution Africa, Asia Northern Europe, North America Japan Rest of Asia Indonesia, China Vietnam, Cambodia Far East Far East Polynesia Australian indigenous population Philippines Europe, Middle East, Egypt, India, Asia Europe, Japan Europe, Asia, South Africa, USA Australia, Japan, Papua New Guinea Sub-Saharan Africa, UK, France Central and South America, Bolivia Brazil, Venezuela, Nicaragua Venezuela, Panama, Columbia Argentina, Bolivia, France USA, Germany, Japan, France USA, Japan, Nicaragua Vietnam, Cambodia Japan
Modified from Locarnini et al. (2013) a PC, precore mutations such as G1896A; BCP, basal core promoter mutations such as A1762T, G1764A; very common (most isolates); common (up to
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