title: Hepatitis C virus-induced autophagy is independent of the unfolded protein response.
abstract: Hepatitis C virus (HCV) has been shown to induce autophagy and the unfolded protein response (UPR), but the mechanistic link between the induction of these two cellular processes remains unclear. We demonstrate here that HCV infection induces autophagy, as judged by accumulation of lipidated LC3-II, and that this induction occurs rapidly after infection, preceding the stimulation of the UPR, which occurs only at later stages, after the viral envelope glycoproteins have been expressed to high levels. Furthermore, both genotype 1b and 2a subgenomic replicons expressing nonstructural (NS3-5B) proteins and JFH-1 virus lacking the envelope glycoproteins potently induced autophagy in the absence of detectable UPR. This ability was also shared by a subgenomic replicon derived from the related GB virus B (GBV-B). We also show that small interfering RNA (siRNA)-mediated silencing of the key UPR inducer, Ire1, has no effect on HCV genome replication or the induction of autophagy, further demonstrating that the UPR is not required for these processes. Lastly, we demonstrate that the HCV replicase does not colocalize with autophagosomes, suggesting that the induction of autophagy is not required to generate the membrane platform for HCV RNA replication.
authors: Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
authors: Bjorn-Patrick
authors: BP
authors: Mohl
authors: Philip R
authors: PR
authors: Tedbury
authors: Stephen
authors: S
authors: Griffin
authors: Mark
authors: M
authors: Harris
mesh_terms: D001343:Autophagy; D002460:Cell Line; D020868:Gene Silencing; D016679:Genome, Viral; D005838:Genotype; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D011489:Protein Denaturation; D017510:Protein Folding; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012093:Replicon / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D056811:Unfolded Protein Response
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012313:RNA