Asialoglycoprotein receptor interacts with the preS1 domain of hepatitis B virus in vivo and in vitro

Background: The preS1 domain of the large envelope protein has been identified as an essential viral structure involved in hepatitis B virus (HBV) attachment. However, the cellular receptor(s) for HBV has not yet been identified. Aims: To identify a cell-surface receptor for HBV, which could elucidate the molecular mechanism of HBV infection. Methods: A novel yeast two-hybrid system was used to screen proteins interacting with the preS1 region of HBV. Their interaction was verified by yeast cotransformation, coimmunoprecipitation and mammalian two-hybrid assay, while their intracellular and tissue localization was analyzed by confocal microscopy and immunohistochemistry, respectively. Results: Asialoglycoprotein receptor (ASGPR) interacted specifically and directly with the preS1 domain of HBV in vivo and in vitro. The levels of expression of preS1 and ASGPR in the liver were similar and correlated with each other. Conclusions: ASGPR is a candidate receptor for HBV that mediates further steps of HBV entry.