Document Detail

Cellular immediate-early gene expression occurs kinetically upstream of Epstein-Barr virus bzlf1 and brlf1 following cross-linking of the B cell antigen receptor in the Akata Burkitt lymphoma cell line.
MedLine Citation:
PMID:  20861250     Owner:  NLM     Status:  MEDLINE    
The Epstein-Barr virus (EBV) lytic activator genes bzlf1 and brlf1 are conventionally referred to as immediate-early (IE) genes. However, previous studies showed that the earliest expression of these genes was blocked by cycloheximide when the EBV lytic cycle was induced by histone deacetylase (HDAC) inhibitors and protein kinase C agonists. Anti-IgG activates a complex signal transduction pathway that leads to EBV lytic activation in the Akata cell line. Here we demonstrate that in Akata cells, where lytic cycle activation occurs very rapidly after anti-IgG treatment, de novo protein synthesis is also required for induction of bzlf1 and brlf1 expression. New protein synthesis is required up to 1.25 h after application of anti-IgG; bzlf1 and brlf1 mRNAs can be detected 1.5 h after anti-IgG. Five cellular IE genes were shown to be expressed by 1 h after addition of anti-IgG, and their expression preceded that of bzlf1 and brlf1. These include early growth response genes (egr1, egr2, and egr3) and nuclear orphan receptors (nr4a1 and nr4a3). These genes were activated by anti-IgG treatment of Akata cells with and without the EBV genome; therefore, their expression was not dependent on expression of any EBV gene product. EGR1, EGR2, and EGR3 proteins were kinetically upstream of ZEBRA and Rta proteins. Expression of EGR1, ZEBRA, and Rta proteins were inhibited by bisindolylmaleimide X, a selective inhibitor of PKC. The findings suggest a revised model in which the signal transduction cascade activated by cross-linking of the B cell receptor induces expression of cellular IE genes, such as early growth response and nuclear orphan receptor genes, whose products, in turn, regulate bzlf1 and brlf1 expression.
Jianjiang Ye; Lyndle Gradoville; George Miller
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-22
Journal Detail:
Title:  Journal of virology     Volume:  84     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2010-12-20     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12405-18     Citation Subset:  IM    
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MeSH Terms
Antibodies, Anti-Idiotypic / pharmacology
Blotting, Northern
Cell Line, Tumor
Cross-Linking Reagents
DNA Primers / genetics
Early Growth Response Transcription Factors / genetics,  metabolism
Gene Expression Regulation / drug effects,  physiology*
Herpesvirus 4, Human / metabolism,  physiology*
Immediate-Early Proteins / genetics,  metabolism*
Microarray Analysis
Plasmids / genetics
Receptors, Antigen, B-Cell / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / physiology*
Trans-Activators / genetics,  metabolism*
Virus Activation / physiology*
Grant Support
Reg. No./Substance:
0/Antibodies, Anti-Idiotypic; 0/BRLF1 protein, Human herpesvirus 4; 0/BZLF1 protein, Herpesvirus 4, Human; 0/Cross-Linking Reagents; 0/DNA Primers; 0/Early Growth Response Transcription Factors; 0/Immediate-Early Proteins; 0/Receptors, Antigen, B-Cell; 0/Trans-Activators; 0/anti-IgG

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