HCV-induced oxidative stress by inhibition of Nrf2 triggers autophagy and favors release of viral particles

摘要: Viruses are known to exploit the autophagic machinery for their own benefit. In case of hepatitis C virus autophagy is induced. As serves as a degradation pathway maintain cellular homeostasis, it activated in response stress such elevated levels reactive oxygen species (ROS). Elevated ROS trigger phosphorylation adaptor protein p62 on Ser349 (pS[349] p62) that involved induction autophagy. Consequently, pS[349] binds with higher affinity Keap1 thereby releasing Nrf2 from complex Keap1. Although released should induce heterodimer sMaf proteins expression Nrf2/ARE-dependent genes, HCV-positive cells no activation cytoprotective genes occurs even though amounts present. cells, free trapped via delocalized at replicon complexes cytoplasmic face ER and therefore prevented its entry into nucleus. Scavenging leads decreased impaired Both, inhibition scavenging result viral particles. Taken together, these data identify an intricate mechanism HCV-dependent Nrf2/ARE-mediated gene which counteracts p62-induced Nrf2. Thereby ROS-levels preserved turn activate favor HCV particle release.