The Hepatitis B Virus Receptor

Abstract

Hepatitis B virus (HBV) infection affects 240 million people worldwide. A liver-specific bile acid transporter named the sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV and its satellite, the hepatitis D virus (HDV). NTCP likely acts as a major determinant for the liver tropism and species specificity of HBV and HDV at the entry level. NTCP-mediated HBV entry interferes with bile acid transport in cell cultures and has been linked with alterations in bile acid and cholesterol metabolism in vivo. The human liver carcinoma cell line HepG2, complemented with NTCP, now provides a valuable platform for studying the basic biology of the viruses and developing treatments for HBV infection. This review summarizes critical findings regarding NTCP's role as a viral receptor for HBV and HDV and discusses important questions that remain unanswered.

Unusual Features of Sodium Taurocholate Cotransporting Polypeptide as a Hepatitis B Virus Receptor

“…Ni et al reported that adding up to 2.5% DMSO to culture medium could increase HBeAg production from ccHBV infected HepG2/NTCP cells by up to 10-fold, which was about 100 times higher than produced by similarly infected HepaRG cells (18). This, combined with the no need for prolonged differentiation, makes HepG2/NTCP cells a more attractive system of in vitro infection (39). However, infection based on NTCP overexpression can be artificial, and the use of an exogenous promoter to drive NTCP expression prevents feedback transcriptional regulation of NTCP expression, which might be operative during the natural course of infection.…”

“…Considering that NTCP is a binding partner for the amino terminus of preS1 domain, it is possible that cytosolic (39), a related question is whether overexpressed NTCP suppresses virion secretion as well. Certainly, NTCP did not appear to markedly inhibit HBV virion secretion when HBV DNA replication was maintained at a high level through the strong CMV promoter (Fig.…”

Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors

“…Fortunately, the viral receptor was conserved in mammal species to a large extent, which may reduce the influence of this bias on the diversity of viral receptors. Secondly, due to the difficulties of identifying viral receptors (Li, 2015b;Pillay et al, 2016;Yan et al, 2012), the database of mammalian virus-host receptor interaction was still limited in its size, which hindered us from a more comprehensive survey of the correlation characteristics between viruses and viral receptors. More effective methods, either experimental or computational (Drayman et al, 2013), should be developed for identifying viral receptors, while the characteristics identified in this study may help such endeavors.…”

Tratamiento actual y nuevas terapias contra la infección crónica por el virus de la Hepatitis B

“…Aunque infecta a otros primates, su principal hospedero es el ser humano y se han identificado 10 genotipos (A-J) con diferente distribución geográfica, comportamiento clínico y respuesta a los tratamientos disponibles (11 El VHB ingresa al hepatocito por endocitosis mediante la interacción del HBsAg con el receptor polipéptido cotransportador de sodio-taurocolato (NTCP), con lo que pierde su envoltura (19,20). La nucleocápside es transportada hasta el núcleo donde su ADN parcial es madurado por proteínas celulares a un ADNccc, el cual es un minicromosoma muy estable que va a servir como modelo transcripcional para la ARN polimerasa II del hospedero (13,21).…”