Article ; Online: Endoplasmic reticulum stress causes EBV lytic replication.
2011 Volume 118, Issue 20, Page(s) 5528–5539
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- ...
| 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. |
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| MeSH term(s) | Carcinogens/pharmacology ; Cell Line ; Cinnamates/pharmacology ; Endoplasmic Reticulum Stress/physiology ; Enzyme Inhibitors/pharmacology ; Epstein-Barr Virus Infections/metabolism ; Epstein-Barr Virus Infections/physiopathology ; Epstein-Barr Virus Infections/virology ; 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 ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/growth & development ; Humans ; Immediate-Early Proteins/genetics ; Lymphocytes/cytology ; Lymphocytes/metabolism ; Lymphocytes/virology ; Lymphoma/metabolism ; Lymphoma/virology ; 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 ; Virus Replication/physiology |
| Chemical Substances | BRLF1 protein, Human herpesvirus 4 ; BZLF1 protein, Herpesvirus 4, Human ; Carcinogens ; Cinnamates ; Enzyme Inhibitors ; Eukaryotic Initiation Factor-2 ; GP 300-350, Epstein-Barr virus ; Immediate-Early Proteins ; Membrane Glycoproteins ; Trans-Activators ; Viral Matrix Proteins ; salubrinal ; Thapsigargin (67526-95-8) ; Thiourea (GYV9AM2QAG) ; Tetradecanoylphorbol Acetate (NI40JAQ945) |
| Language | English |
| Publishing date | 2011-08-17 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 80069-7 |
| ISSN | 1528-0020 ; 0006-4971 |
| ISSN (online) | 1528-0020 |
| ISSN | 0006-4971 |
| DOI | 10.1182/blood-2011-04-347112 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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