PMID- 21849482
OWN - NLM
STAT- MEDLINE
DCOM- 20120116
LR  - 20211020
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 118
IP  - 20
DP  - 2011 Nov 17
TI  - Endoplasmic reticulum stress causes EBV lytic replication.
PG  - 5528-39
LID - 10.1182/blood-2011-04-347112 [doi]
AB  - 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.
FAU - Taylor, Gwen Marie
AU  - Taylor GM
AD  - Department of Pathology, University of Pittsburgh and Children's Hospital of 
      Pittsburgh, Pittsburgh, PA, USA.
FAU - Raghuwanshi, Sandeep K
AU  - Raghuwanshi SK
FAU - Rowe, David T
AU  - Rowe DT
FAU - Wadowsky, Robert M
AU  - Wadowsky RM
FAU - Rosendorff, Adam
AU  - Rosendorff A
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110817
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (BRLF1 protein, Human herpesvirus 4)
RN  - 0 (BZLF1 protein, Herpesvirus 4, Human)
RN  - 0 (Carcinogens)
RN  - 0 (Cinnamates)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (GP 300-350, Epstein-Barr virus)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (salubrinal)
RN  - 67526-95-8 (Thapsigargin)
RN  - GYV9AM2QAG (Thiourea)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Carcinogens/pharmacology
MH  - Cell Line
MH  - Cinnamates/pharmacology
MH  - Endoplasmic Reticulum Stress/*physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Epstein-Barr Virus Infections/metabolism/physiopathology/*virology
MH  - Eukaryotic Initiation Factor-2/metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Viral/physiology
MH  - Genes, Immediate-Early/genetics
MH  - Germinal Center/cytology/metabolism/virology
MH  - Herpesvirus 4, Human/drug effects/*genetics/*growth & development
MH  - Humans
MH  - Immediate-Early Proteins/genetics
MH  - Lymphocytes/cytology/metabolism/virology
MH  - Lymphoma/metabolism/*virology
MH  - Membrane Glycoproteins/genetics
MH  - Plasma Cells/cytology/metabolism/virology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Thapsigargin/pharmacology
MH  - Thiourea/analogs & derivatives/pharmacology
MH  - Trans-Activators/genetics
MH  - Viral Matrix Proteins/genetics
MH  - Virus Replication/drug effects/*physiology
PMC - PMC3217354
EDAT- 2011/08/19 06:00
MHDA- 2012/01/17 06:00
PMCR- 2011/11/17
CRDT- 2011/08/19 06:00
PHST- 2011/08/19 06:00 [entrez]
PHST- 2011/08/19 06:00 [pubmed]
PHST- 2012/01/17 06:00 [medline]
PHST- 2011/11/17 00:00 [pmc-release]
AID - S0006-4971(20)40330-1 [pii]
AID - 2011/347112 [pii]
AID - 10.1182/blood-2011-04-347112 [doi]
PST - ppublish
SO  - Blood. 2011 Nov 17;118(20):5528-39. doi: 10.1182/blood-2011-04-347112. Epub 2011 
      Aug 17.