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lüll Endoplasmic reticulum stress causes EBV lytic replication Taylor GM; Raghuwanshi SK; Rowe DT; Wadowsky RM; Rosendorff ABlood 2011[Nov]; 118 (20): 5528-39Endoplasmic reticulum (ER) stress triggers a homeostatic cellular response in mammalian cells to ensure efficient folding, sorting, and processing of client proteins. In lytic-permissive lymphoblastoid cell lines (LCLs), pulse exposure to the chemical ER-stress inducer thapsigargin (TG) followed by recovery resulted in the activation of the EBV immediate-early (BRLF1, BZLF1), early (BMRF1), and late (gp350) genes, gp350 surface expression, and virus release. The protein phosphatase 1 a (PP1a)-specific phosphatase inhibitor Salubrinal (SAL) synergized with TG to induce EBV lytic genes; however, TG treatment alone was sufficient to activate EBV lytic replication. SAL showed ER-stress-dependent and -independent antiviral effects, preventing virus release in human LCLs and abrogating gp350 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated B95-8 cells. TG resulted in sustained BCL6 but not BLIMP1 or CD138 expression, which is consistent with maintenance of a germinal center B-cell, rather than plasma-cell, phenotype. Microarray analysis identified candidate genes governing lytic replication in LCLs undergoing ER stress.|Carcinogens/pharmacology[MESH]|Cell Line[MESH]|Cinnamates/pharmacology[MESH]|Endoplasmic Reticulum Stress/*physiology[MESH]|Enzyme Inhibitors/pharmacology[MESH]|Epstein-Barr Virus Infections/metabolism/physiopathology/*virology[MESH]|Eukaryotic Initiation Factor-2/metabolism[MESH]|Gene Expression Profiling[MESH]|Gene Expression Regulation, Viral/physiology[MESH]|Genes, Immediate-Early/genetics[MESH]|Germinal Center/cytology/metabolism/virology[MESH]|Herpesvirus 4, Human/drug effects/*genetics/*growth & development[MESH]|Humans[MESH]|Immediate-Early Proteins/genetics[MESH]|Lymphocytes/cytology/metabolism/virology[MESH]|Lymphoma/metabolism/*virology[MESH]|Membrane Glycoproteins/genetics[MESH]|Plasma Cells/cytology/metabolism/virology[MESH]|Tetradecanoylphorbol Acetate/pharmacology[MESH]|Thapsigargin/pharmacology[MESH]|Thiourea/analogs & derivatives/pharmacology[MESH]|Trans-Activators/genetics[MESH]|Viral Matrix Proteins/genetics[MESH]|Virus Replication/drug effects/*physiology[MESH] |