title: Look who's talking-the crosstalk between oxidative stress and autophagy supports exosomal-dependent release of HCV particles.
abstract: Autophagy is a highly conserved and regulated intracellular lysosomal degradation pathway that is essential for cell survival. Dysregulation has been linked to the development of various human diseases, including neurodegeneration and tumorigenesis, infection, and aging. Besides, many viruses hijack the autophagosomal pathway to support their life cycle. The hepatitis C virus (HCV), a major cause of chronic liver diseases worldwide, has been described to induce autophagy. The autophagosomal pathway can be further activated in response to elevated levels of reactive oxygen species (ROS). HCV impairs the Nrf2/ARE-dependent induction of ROS-detoxifying enzymes by a so far unprecedented mechanism. In line with this, this review aims to discuss the relevance of HCV-dependent elevated ROS levels for the induction of autophagy as a result of the impaired Nrf2 signaling and the described crosstalk between p62 and the Nrf2/Keap1 signaling pathway. Moreover, autophagy is functionally connected to the endocytic pathway as components of the endosomal trafficking are involved in the maturation of autophagosomes. The release of HCV particles is still not fully understood. Recent studies suggest an involvement of exosomes that originate from the endosomal pathway in viral release. In line with this, it is tempting to speculate whether HCV-dependent elevated ROS levels induce autophagy to support exosome-mediated release of viral particles. Based on recent findings, in this review, we will further highlight the impact of HCV-induced autophagy and its interplay with the endosomal pathway as a novel mechanism for the release of HCV particles.
authors.affiliation: Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Medvedev
authors.affiliation: Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany.|Deutsches Zentrum für Infektionsforschung (DZIF), Gießen, Marburg, Langen, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Hildt
authors.affiliation: Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany. daniela.ploen@pei.de.
authors.forename: Daniela
authors.identifier: 0000-0002-8991-126X
authors.initials: D
authors.lastname: Ploen
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D063326:Exosome Multienzyme Ribonuclease Complex / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D063326:Exosome Multienzyme Ribonuclease Complex
keywords: Autophagy; Endosomal/exosomal trafficking; Hepatitis C virus; Nrf2/Keap1-signaling; Reactive oxygen species (ROS); p62