Study of the Endocytosis and Intracellular Localization of Subviral Particles of Hepatitis B Virus in Primary Hepatocytes

Although our knowledge of the hepatitis B virus (HBV) life cycle has increased tremendously during the past 20 yr, the early steps of human HBV infection are still poorly understood. This is partly caused by the lack of a suitable cell culture system. Established hepatoma cell lines (e.g., HepG2 or Huh7) are not susceptible at all and proposed receptors for HBV have failed to support HBV entry to date. Because HBV is strictly hepatotropic, cultures of primary human hepatocytes are suitable for elucidation of the entry process of HBV, but very difficult to obtain and handle. Many insights into hepadnaviral uptake have come from the study of duck hepatitis B virus (DHBV) infection in primary duck hepatocytes. The characterization of a primary receptor of DHBV (1 ) and recombinant expression in nonsusceptible cell lines has shown that DHBV is taken up via endocytic vesicles (2 ). Use of labeled DHBV virions from sera of infected ducks for uptake experiments using confocal microscopy has greatly improved the possibilities of studying the endocytic distribution of DHBV virions during infection.