Infection of a human hepatoma cell line by hepatitis B virus

TLDR

No established human hepatoma cell line has been shown susceptible to HBV infection. The study aims to use HepaRG cells to investigate HBV entry mechanisms. HepaRG cells remain differentiated and HBV‑susceptible only in the presence of corticoids and DMSO, and infection specificity was confirmed by neutralizing antibodies and peptide competition. HepaRG cells exhibit hepatocyte‑like morphology, express specific functions, support HBV infection, and closely resemble normal hepatocytes, making them useful for drug metabolism studies.

Abstract

Among numerous established human hepatoma cell lines, none has been shown susceptible to hepatitis B virus (HBV) infection. We describe here a cell line, called HepaRG, which exhibits hepatocyte-like morphology, expresses specific hepatocyte functions, and supports HBV infection as well as primary cultures of normal human hepatocytes. Differentiation and infectability are maintained only when these cells are cultured in the presence of corticoids and dimethyl sulfoxide. The specificity of this HBV infection model was ascertained by both the neutralization capacity of HBV-envelope protein-specific antibodies and the competition with an envelope-derived peptide. HepaRG cells therefore represent a tool for deciphering the mechanism of HBV entry. Moreover, their close resemblance to normal human hepatocytes makes them suitable for many applications including drug metabolism studies.