A cellular protein which binds hepatitis B virus but not hepatitis B surface antigen.

Abstract

The envelope of hepatitis B virus (HBV) consists of three related proteins known as the large (L), middle (M) and small (S) hepatitis B surface antigens (HBsAg). L-HBsAg has a 108-119 amino acid extension at the N terminus compared with M-HBsAg and contains the preS1 sequence of the HBV envelope. Previous research has identified this region as the likely virus attachment protein which is thought to interact with the cellular receptor for the virus. However, as the receptor has still not been identified unequivocally, we used the preS1 region of L-HBsAg to screen a human liver cDNA library by the yeast two-hybrid system. Several positive clones were isolated which encoded cellular proteins that interacted with the HBV preS1 protein. The specificity was examined in an independent manner in experiments in which baculovirus-derived glutathione S-transferase (GST)-preS1 was incubated with 35 S-labelled protein expressed by in vitro translation from the positive clones. The intensity of the interactions using this alternative approach mirrored those observed in the yeast two-hybrid system and two proteins (an unidentified protein and a mitochondrial protein) were selected for further study. The specificity of the binding reaction between the preS1 protein and these two proteins was further confirmed in a competition assay ; HBV purified from serum, but not purified HBsAg, was able to compete with preS1 and thus block GST-preS1 binding to the unidentified protein but not to the mitochondrial protein. The unidentified protein was then expressed as a fusion protein with GST and this was able to bind HBV virions in a direct manner.

NACA as a Potential Cellular Target of Hepatitis B Virus PreS1 Protein

“…Recently, entry of duck hepatitis B virus initiated by its preS subdomain with a cellular entry receptor, carboxypeptidase D (CPD; gp180), has been reported (6). Many potential cellular preS1 receptors have been reported, including human immunoglobulin A, interleukin 6, glyceraldehyde-3-phosphate dehydrogenase, apolipoprotein H, asialoglycoprotein receptor, a clathrin adapter-related protei, and an 80-kD glycoprotein on human hepatocytes (7)(8)(9). But until now, there has been no reliable information on the receptor for HBV.…”

The HBV web: An insight into molecular interactomes between the hepatitis B virus and its host en route to hepatocellular carcinoma

“…Another study identified multiple LHBsAg interactors among which human pigment epithelium-differentiation factor (PEDF), human hypoxanthine phosphoribosyl transferase (HPRT), Human X-box binding protein-1 (XBP-1) are mentionable. 99 Notably, all these proteins differentially regulate the fine balance between cellular proliferation, stress response and death in the course of carcinogenesis. During viral replication, surface protein accumulates in the ER that leads to HCC prevalence.…”

“…The LHBsAg protein, through its pre‐S1 domain physically interacts with the ear domain of γ2‐adaptin protein 98 and mediates viral biogenesis, such as HBV assembly. Another study identified multiple LHBsAg interactors among which human pigment epithelium‐differentiation factor (PEDF), human hypoxanthine phosphoribosyl transferase (HPRT), Human X‐box binding protein‐1 (XBP‐1) are mentionable 99 . Notably, all these proteins differentially regulate the fine balance between cellular proliferation, stress response and death in the course of carcinogenesis.…”