Untersuchungen zu Interaktionen des Hepatitis A-Virus mit zellulären antiviralen Mechanismen

Abstract

Hepatitis A virus (HAV) infection in vitro results in a persistent noncytopathic infection during which the viral replication is downregulated. This adjustment of HAV replication to a moderate level may contribute to the development and maintenance of persistence in cell culture and the propagation of HAV in vivo. In order to investigate the underlying mechanism, different cellular antiviral systems were examined. A possible replication control via HAV dependent induction of MxA or ISG20 gene expression could be excluded, whereas an investigation of the 2',5'-oligoadenylate synthetase/RNase L system showed obscure results. HAV upregulates RNase L expression at later stages of infection, resulting in an enhanced potential to activate RNase L in persistently infected cells. However, replication kinetics during differential expression of RNase L showed no impact on HAV titre, whereas the establishment of HAV infection in individual cells was partly blocked by RNase L overexpression.