Inhibition zellulärer antiviraler Abwehrmechanismen durch das Hepatitis A-Virus - eine Analyse der beteiligten viralen Faktoren: Inhibition des IRF-3 -vermittelten Signalweges durch das Nichtstrukturprotein 2B des Hepatitis A-Virus

Abstract

Hepatitis A virus (HAV) antagonizes the innate immune response by inhibition of Newcastle disease virus (NDV)- or dsRNA-mediated interferon-beta (IFN-beta) gene expression. The aim of this dissertation was to investigate which viral properties or factors are involved in this suppression. It could be demonstrated that the nonstructural protein HAV-2B correlates with the ability of HAV to suppress the NDV- or dsRNA-mediated interferon-beta (IFN-beta) gene expression. Further investigations supported this finding that HAV-2B is involved in inhibition of activation of transcription factor IRF-3 by HAV. As IRF-3 is necessary for IFN-beta transcription, inhibition of this factor results in efficient suppression of IFN-beta synthesis. This ability might be of vital importance for HAV, which is an exceptionally slowly growing virus sensitive to IFN-beta, as it allows this virus to establish infection and maintain viral replication for a longer time.