Chronic infection with the human Hepatitis B virus is a global health problem and a main cause of progressive liver diseases.
Hepatitis B virus exhibits a narrow host range, replicating primarily in hepatocytes.
Both host and hepatocyte specificity presumably involve specific receptor interactions on the target cell.
However, direct evidence for this hypothesis is missing.
Following the observation that Hepatitis B virus entry is specifically blocked by L-protein-derived preS1-lipopeptides, Dr Anja Meier and colleagues from Germany visualized specific human hepatitis B virus receptor/ligand complexes on hepatic cells and quantified the turnover kinetics.
|Hep B virus hepatotropism is mediated by the highly selective expression of a yet unknown receptor|
The team evaluated fluorescein isothiocyanate-labeled, myristoylated human Hepatitis B virus preS1-peptides.
The researchers demonstrated the presence of a highly specific human Hepatitis B virus receptor on the plasma membrane of human Hepatitis B virus-susceptible primary human and tupaia hepatocytes and HepaRG cells.
The team also observed the receptor on hepatocytes from the nonsusceptible species mouse, rat, rabbit and dog; the requirement of a differentiated state of the hepatocyte for specific preS1-binding; the lack of detectable amounts of the receptor on HepG2 and HuH7 cells a slow receptor turnover at the hepatocyte membrane; and an association of the receptor with actin microfilaments.
The presence of the preS1-receptor in primary hepatocytes from some non-human hepatitis B virus-susceptible species indicates that the lack of susceptibility of these cells is owed to a postbinding step.
Dr Meier's team comments, "These findings suggest that Hepatitis B virus hepatotropism is mediated by the highly selective expression of a yet unknown receptor on differentiated hepatocytes, while species specificity of the Hepatitis B virus infection requires selective downstream events, e.g., the presence of host dependency or the absence of host restriction factors."
"The criteria defined here will allow narrowing down reasonable receptor candidates and provide a binding assay for Hepatitis B virus-receptor expression screens in hepatic cells."