Protein disulfide isomerases (PDIs) catalyze disulfide bond formation between protein cysteine residues during protein folding in the endoplasmic reticulum (ER) lumen and are essential for maintaining ER homoeostasis. The life cycle of the hepatitis C virus (HCV) is closely associated with the ER. Synthesis and maturation of HCV proteins occur in the ER membrane and are mediated by multiple host cell factors that include also PDI. Here, we present a study investigating the effect of PDI inhibition on Huh7 human hepatoma cells harboring an HCV subgenomic replicon using the abscisic acid-derived PDI inhibitor origamicin. Transcriptional profiling shows that origamicin changed the expression levels of genes involved in the oxidative and ER stress responses and the unfolded protein response, as indicated by the upregulation of antioxidant enzymes and chaperone proteins, the downregulation of cell-cycle proteins, and induction of apoptosis-associated genes. Our data suggest that origamicin negatively impacts HCV replication by causing an imbalance in cellular homoeostasis and induction of stress responses. These insights suggest that inhibition of PDIs by low-molecular-weight inhibitors could be a promising approach to the discovery of novel antiviral compounds.
Pubmed ID: 30775641 RIS Download
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View all literature mentionsGeneAnnot provides a revised and improved annotation of Affymetrix probe-sets from HG-U95, HG-U133 and HG-U133 Plus2.0. Probe-sets are related to GeneCards genes, by direct sequence comparison of probes to GenBank, RefSeq and Ensembl mRNA sequences, while assigning sensitivity and specificity scores to each probe-set to gene match. Where such matches are not found, probe-sets are annotated by their relation to GenBank mRNA sequences and UniGene clusters. The results are integrated with the GeneCards, GeneLoc and GeneNote databases. HG-U95, HG-U133, HG-U133
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View all literature mentionsCell line Huh-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
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