Endothelial cell-mediated uptake of a hepatitis B virus: A new concept of liver targeting of hepatotropic microorganisms

The liver is a target for many infectious agents, most notably hepatitis vi ruses. However, several receptor molecules identified so far for hepatitis viruses were found to be ubiquitously expressed and can thus not account fo r efficient liver targeting. Using a model hepatitis B virus, the duck hepa titis B virus (DHBV), we have obtained data indicating that scavenging live r sinusoidal endothelial cells (LSEC), rather than hepatocytes themselves, play the key role in the initial uptake of viral pathogens into the liver. Experiments with fluorescent viral particles and coated gold particles in t est animals, as well as in primary liver cell culture, demonstrated a prefe rential uptake of the viral substrates into LSEC. Intracellularly, fluoresc ent virus particles internalized by LSEC colocalized with the DHBV receptor , carboxypeptidase D, suggesting receptor-mediated rescue from lysosomal de gradation. To comply with the high efficiency by which hepatitis B viruses infect hepatocytes in vivo, we propose that viruses initially scavenged by LSEC are thereafter released to infect adjacent hepatocytes, the only cells capable of replicating these viruses. Such a model of primary uptake into LSEC may illustrate a general mechanism by which blood-borne hepatotropic a gents are targeted to the hepatocytes in the liver.