Untersuchungen zum Gewebetropismus des Hepatitis A-Virus im Mausmodell durch quantitative Analyse viraler Nukleinsäure

Abstract

Hepatitis A virus (HAV) is transmitted by the faecal-oral route, its target for replication is the liver. The mechanisms underlying the hepatotropism of HAV and the relapsing courses of infections are unknown. Immunoglobulin A is generated early after infection and often HAV virions are partially associated with IgA molecules. As the liver plays a central role in IgA metabolism by eliminating IgA as well as antigen-IgA complexes, we wondered if HAV-specific IgA ligated to HAV supports the targeting of HAV to the liver. HAV-anti-HAV IgA complexes can be translocated from the intestinal lumen into blood via the epithelial polymeric immunoglobulin receptor (pIgR) and the immunoglobulin complexes are infectious for human hepatocytes via the IgA-specific hepatocellular asialoglycoprotein receptor (ASGPR). This study shows an in vivo IgA-mediated HAV infection of the liver from blood using a mouse model. HAV RNA in the liver was significantly reduced in immunized mice showing that high avidity anti-HAV IgG antibodies protected not only against an HAV infection but also against an infection by HAV/IgA complexes.