Die molekulare Interaktion von Proteinen des Hepatitis A-Virus mit zellulären Membranen und dem Cytoskelett

Abstract

Hepatitis A virus (HAV) is a hepatotrophic picornavirus. Exosome-like structures are involved in basolateral HAV release into blood. In contrast, nothing is known about the apical release of the virus in the intestinal tract via bile. Also the site and the mechanisms involved in HAV maturation are not known. By analysing interactions of expressed HAV proteins in cell culture, I found that HAV is able to block the classical cellular secretory pathway by modifying structures involved in ER-to-Golgi transport and inhibiting this transport in general. As an alternative pathway HAV seems to recruit lysosome-related organelles. HAV accumulated inside these organelles which are also detectable in close proximity to the plasma membrane. Inhibition of lysosomal exocytosis inhibited the release of HAV. The viral proteins 3AB and 3ABC, which associate with lysosomes, might participate in recruiting lysosomal membranes. Furthermore, maturation cleavage of the structural precursor VP1-2A takes places in these organelles. Knock-down of Cathepsin L inhibited this cleavage event. HAV might gain access to lysosomes by autophagosomes. HAV-3A was found in association with these organelles and in the presents of HAV-2B autophagosomes were induced.