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.

Quantitative Proteomic Analysis Reveals That Arctigenin Alleviates Concanavalin A-Induced Hepatitis Through Suppressing Immune System and Regulating Autophagy

“…HBV and HCV could induce accumulations of autophagosome and p62 but impair lysosomal acidification, leading to incomplete autophagy in autophagic degradation ( 126 , 127 ). HCV-induced oxidative stress triggered p62-dependent autophagy and interplayed with exosomes to mediate the release of HCV particles ( 128 , 129 ). Epigallocatechin-3-gallate inhibited HBV replication by resisting insufficient autophagy and enhancing lysosomal acidification ( 130 ).…”

Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process

“…Notably, HCV RNA containing exosomes have been reported [137][138][139][140][141]. However, whether and to what extent these exosomes transmit replication competent HCV genomes, proteins and/or virions remains a matter of debate [132,140,142].…”

Bicyclol Attenuates Acute Liver Injury by Activating Autophagy, Anti-Oxidative and Anti-Inflammatory Capabilities in Mice

“…Autophagy comprises membrane biogenesis and formation of the autophagosome, which sequesters a region of cytosol and/or an entire organelle and subsequently fuses with the lysosome for degradation of its contents (Mizushima et al, 2008). Recently, modulation of the oxidative stress and autophagy crosstalk has been shown to be a new therapeutic target (Medvedev et al, 2017). Moreover, inflammation is often accompanied with formation of reactive oxygen species (ROS) and oxidative stress.…”