Interaction between desialylated hepatitis B virus and asialoglycoprotein receptor on hepatocytes may be indispensable for viral binding and entry

Abstract

The cellular receptor for hepatitis B virus (HBV) infection has not yet been identified. The purpose of this study was to address the possibility of participation by desialylated HBV and the asialoglycoprotein receptor (ASGP-R) exclusively expressed on liver parenchymal cells, in infection. Assays for viral binding and entry were performed by culturing a hepatoblastoma cell line, HepG2, and HBV particles derived from the HBV carrier in the presence or absence of neuraminidase (NA). Viral binding and entry were clearly enhanced in the presence of NA, and the enhancement of the binding could be blocked by asialo-fetuin and ethylenediamine-tetraacetic acid (EDTA). In addition, covalently closed circular (CCC)-DNA, as a marker of infectivity, was detected in the presence of NA, but not in its absence. The optimal concentration of NA raised infectivity more than 1000 times. We concluded that this method makes it feasible to evaluate the infectivity of HBV in vitro and that ASGP-R may be a specific HBV receptor once viral particles are desialylated.

Role of glycosaminoglycans for binding and infection of hepatitis B virus

“…Although DHBV shares many molecular similarities with HBV, DHBV probably uses other receptors for primary attachment than GAGs (for a recent review, see Glebe and Urban, 2007). In a recent publication, Owada et al (2006) reported that treatment of HBV with sialidase during incubation with human hepatoma cell line HepG2 would result in infection via the ASGPR, a liver-specific lectin that is responsible for uptake of desialylated glycoproteins from blood into hepatocytes (Spiess, 1990) and has been proposed as a receptor for HBV (Treichel et al, 1994;1997). In previous studies, we could show that Nand O-glycans of HBV surface glycoproteins could be desialylated by treatment with sialidase (Schmitt et al, 1999;, resulting in increased binding to HepG2 cells .…”

“…The removal of the distinct sugars from cell-surface proteins was tested by shifting of the heavily N-glycosylated and sialylated asialoglycoprotein receptor (ASGPR) in SDS-PAGE immunoblots from plasmamembrane preparations of PTH (data not shown). Because the ASGPR is a liver-specific lectin, it had been speculated that it might serve as a specific receptor for HBV, especially during treatment of hepatocytes with sialidase (Owada et al, 2006). However, neither preincubation with sialidase, nor incubation in the presence of sialidase, resulted in significant increase or decrease of infection (Fig.…”

Viral infection can induce the production of autoantibodies

“…It is still unknown how long this antibody will persist in patients with chronic HBV and if Anti-asialoglycoprotein receptor-R [41] The asialoglycoprotein receptor is a liver specific glycoprotein of the cell membrane. Its main function is the internalization of asialoglycoproteins by binding a terminal galactose residue to coated pits [47]. Anti-asialoglycoprotein receptor-R may be a specific receptor for hepatitis B virus infection [48].…”

Characterization of Hepatitis B virus (HBV) genotypes in patients from Rondônia, Brazil

“…HBV infection results in 500,000 to 1.2 million deaths per year caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma and is the 10 th leading cause of death worldwide [3]. The mechanisms for persistent HBV infection are not fully understood, but they seem to involve several aspects, including genetic components [4]. The role of genetics components of the virus and the host in the natural history of hepatitis B including HBV genotypes and subgenotypes; basal core promoter and pre core mutations; HBV DNA serum levels and co-infection with other viruses (particularly hepatitis C and human immunodefficiency viruses) have been recently reviewed [5].…”