Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
HBV is a DNA virus that coevolved with humans.1 Different from many other viruses that are detected only after amplification of their genetic material, HBV is characterised by the production of a progeny of infectious virions, but also of high concentrations (5–10 μg/mL) of viral proteins.
These proteins are ‘byproducts’ of the synthesis of the proteins coded by HBV core and HBV pre-S1, pre-S2 and S genes, the building blocks of the nucleocapsid (the internal part of the virus containing HBV–DNA) and of the HBV envelope. The proteins derived from the nucleocapsid gene and defined as HBcrAg are composed of truncated or immature forms of the nucleocapsid protein: the HBeAg (defined also as p17, a fully secreted form of truncated nucleoprotein), p22 (a longer version of p17) and HBcAg (incomplete core particles, a ‘naked’ HBV).2 The pre-S1, pre-S2 and S gene products are instead envelope components of the mature HBV virions but they are produced in large excess thereby giving rise also to a large quantity of defective non-infectious particles (spheres and filaments) (detailed molecular description reviewed in Bruss3). These non-infectious viral proteins (both HBcrAg and HBsAg) are secreted into the blood stream, impact host immunity and likely allow HBV to persist in humans more efficiently. For example, HBeAg appears (in animal models) to play a role in the suppression of nucleocapsid-specific T cells in vertical infection.4 The defective particles that constitute HBsAg have been instead hypothesised to have a broader effect on the host antiviral immunity. Defective particles act primarily as a decoy for protective anti-HBs antibodies, since they outnumber the infectious virions by 103–106-fold5 and can bind anti-HBs antibodies. HBsAg is also associated with selective defects of HBs-specific …
Contributors Both authors wrote the commentary.
Funding This work was supported by a Singapore Translational Research investigator award to AB (MOH-000019(MOH-StaR17Nov-0001).
Competing interests AB declares the following relationship with commercial entities developing therapeutics for HBV treatment. He acted as a consultant and served on the advisory boards of Assembly Biosciences, Gilead Sciences, Roche, Jansseen-Cilag, Vir, Molecular Therapies and HUMABS BioMed. AB is also a co-founder of LION TCR Pte. a biotech company developing T-cell receptors for treatment of virus-related cancers and chronic viral diseases.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Commissioned; internally peer reviewed.