Antiviral Res. 2018 Jul 27. pii: S0166-3542(17)30816-1. doi: 10.1016/j.antiviral.2018.07.019. [Epub ahead of print]
Hepatitis B virus: The challenge of an ancient virus with multiple faces and a remarkable replication strategy.
Caballero A1, Tabernero D2, Buti M3, Rodríguez-Frías F4.
Author information
1
Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona (UAB), 119-129 Passeig Vall, d'Hebron, Clinical Laboratories, 08035 Barcelona, Spain. Electronic address: [email protected].
2
Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona (UAB), 119-129 Passeig Vall, d'Hebron, Clinical Laboratories, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 3-5 Avenida Monforte de Lemos, pavilion 11, 28029 Madrid, Spain. Electronic address: [email protected].
3
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 3-5 Avenida Monforte de Lemos, pavilion 11, 28029 Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona (UAB), 119-129 Passeig Vall d'Hebron, General Hospital, Internal Medicine 2, 08035 Barcelona, Spain. Electronic address: [email protected].
4
Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona (UAB), 119-129 Passeig Vall, d'Hebron, Clinical Laboratories, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 3-5 Avenida Monforte de Lemos, pavilion 11, 28029 Madrid, Spain. Electronic address: [email protected].
Abstract
The hepatitis B virus (HBV) is the prototype member of the Hepadnaviridae, an ancient family of hepatotropic DNA viruses, which may have originated from 360 to 430 million years ago and with evidence of endogenization in reptilian genomes >200 million years ago. The virus is currently estimated to infect more than 250 million humans. The extremely successful spread of this pathogen among the human population is explained by its multiple particulate forms, effective transmission strategies (particularly perinatal transmission), long induction period and low associated mortality. These characteristics confer selective advantages, enabling the virus to persist in small, disperse populations and spread worldwide, with high prevalence rates in many countries. The HBV replication strategy is remarkably complex and includes a multiplicity of particulate structures. In addition to the common virions containing DNA in a relaxed circular (rcDNA) or double-stranded linear (dslDNA) forms, the viral population includes virion-like particles containing RNA or "empty" (viral envelopes and capsids without genomes), subviral particles (only an envelope) and even naked capsids. Consequently, several forms of the genome coexist in a single infection: (i) the "traveler" forms found in serum, including rcDNA and dslDNA, which originate from retrotranscription of a messenger RNA (the pregenomic RNA, another form of the viral genome itself) and (ii) forms confined to the host cell nucleus, including covalently closed circular DNA (cccDNA), which leads to a minichromosome form associated with histones and viral proteins, and double-stranded DNA integrated into the host genome. This complex composition lends HBV a kind of "multiple personality". Are these additional particles and genomic forms simple intermediaries/artifacts or do they play a role in the viral life cycle?
KEYWORDS:
Chronic hepatitis B; Hepadnaviridae; Hepatitis B virus; Vertical transmission; Viral life cycle