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Endoplasmic reticulum stress causes EBV lytic replication.
- Source :
-
Blood [Blood] 2011 Nov 17; Vol. 118 (20), pp. 5528-39. Date of Electronic Publication: 2011 Aug 17. - Publication Year :
- 2011
-
Abstract
- Endoplasmic 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.
- Subjects :
- Carcinogens pharmacology
Cell Line
Cinnamates pharmacology
Enzyme Inhibitors pharmacology
Epstein-Barr Virus Infections metabolism
Epstein-Barr Virus Infections physiopathology
Eukaryotic Initiation Factor-2 metabolism
Gene Expression Profiling
Gene Expression Regulation, Viral physiology
Genes, Immediate-Early genetics
Germinal Center cytology
Germinal Center metabolism
Germinal Center virology
Herpesvirus 4, Human drug effects
Humans
Immediate-Early Proteins genetics
Lymphocytes cytology
Lymphocytes metabolism
Lymphocytes virology
Lymphoma metabolism
Membrane Glycoproteins genetics
Plasma Cells cytology
Plasma Cells metabolism
Plasma Cells virology
Tetradecanoylphorbol Acetate pharmacology
Thapsigargin pharmacology
Thiourea analogs & derivatives
Thiourea pharmacology
Trans-Activators genetics
Viral Matrix Proteins genetics
Virus Replication drug effects
Endoplasmic Reticulum Stress physiology
Epstein-Barr Virus Infections virology
Herpesvirus 4, Human genetics
Herpesvirus 4, Human growth & development
Lymphoma virology
Virus Replication physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 118
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 21849482
- Full Text :
- https://doi.org/10.1182/blood-2011-04-347112