Laboratory Models of Hepatitis B and D Viruses: Search for Cell Permissiveness and Restriction Factors

Hepatitis B virus (HBV is a widely spread human pathogen that accounts for 250 mln cases of chronic hepatitis worldwide. Hepatitis delta virus (HDV) is its viroid-like satellite that substantially aggravates liver disease. Importantly, both HBV and HDV are oncogenic viruses. The development of new antivirals and investigation of virus pathogenesis is limited by absence of effective cellular and animal models. Currently used cell models are based on human primary hepatocytes, liver progenitor HepaRG cells, hepatocyte-like cells derived from iPS or various hepatoma cells overexpressing putative NTCP receptor. However, in most of these models a majority of cells are non-permissive. In this review we briefly review these models, summarize approaches to increase infection rates, and discuss data about proviral and antiviral (restriction) host factors. The data discussed suggest that rates of HBV and HDV infection are limited by hepatocyte polarization, insufficient expression of the NTPC receptor as well as existence of additional co-receptors and restriction factors that can act mostly on virus entry stage.