Document Detail

Epstein-Barr virus (EBV) Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.
MedLine Citation:
PMID:  21423768     Owner:  NLM     Status:  MEDLINE    
Epstein-Barr virus (EBV) Rta belongs to a lytic switch gene family that is evolutionarily conserved in all gamma-herpesviruses. Emerging evidence indicates that cell cycle arrest is a common means by which herpesviral immediate-early protein hijacks the host cell to advance the virus's lytic cycle progression. To examine the role of Rta in cell cycle regulation, we recently established a doxycycline (Dox)-inducible Rta system in 293 cells. In this cell background, inducible Rta modulated the levels of signature G1 arrest proteins, followed by induction of the cellular senescence marker, SA-β-Gal. To delineate the relationship between Rta-induced cell growth arrest and EBV reactivation, recombinant viral genomes were transferred into Rta-inducible 293 cells. Somewhat unexpectedly, we found that Dox-inducible Rta reactivated both EBV and Kaposi's sarcoma-associated herpesvirus (KSHV), to similar efficacy. As a consequence, the Rta-mediated EBV and KSHV lytic replication systems, designated as EREV8 and ERKV, respectively, were homogenous, robust, and concurrent with cell death likely due to permissive lytic replication. In addition, the expression kinetics of EBV lytic genes in Dox-treated EREV8 cells was similar to that of their KSHV counterparts in Dox-induced ERKV cells, suggesting that a common pathway is used to disrupt viral latency in both cell systems. When the time course was compared, cell cycle arrest was achieved between 6 and 48 h, EBV or KSHV reactivation was initiated abruptly at 48 h, and the cellular senescence marker was not detected until 120 h after Dox treatment. These results lead us to hypothesize that in 293 cells, Rta-induced G1 cell cycle arrest could provide (1) an ideal environment for virus reactivation if EBV or KSHV coexists and (2) a preparatory milieu for cell senescence if no viral genome is available. The latter is hypothetical in a transient-lytic situation.
Yen-Ju Chen; Wan-Hua Tsai; Yu-Lian Chen; Ying-Chieh Ko; Sheng-Ping Chou; Jen-Yang Chen; Su-Fang Lin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-10
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-03-22     Completed Date:  2011-07-05     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e17809     Citation Subset:  IM    
College of Medicine, Graduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan.
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MeSH Terms
Cell Death / drug effects
Cell Line
Cell Line, Tumor
Cell Proliferation / drug effects
Doxycycline / pharmacology
G1 Phase / drug effects,  genetics
Gene Expression Regulation, Viral / drug effects
Herpesvirus 4, Human / drug effects,  genetics,  physiology*
Herpesvirus 8, Human / drug effects,  genetics,  physiology*
Immediate-Early Proteins / genetics
Nasopharyngeal Neoplasms / genetics,  pathology
Time Factors
Viral Proteins / metabolism*
Virus Activation / drug effects,  physiology*
Virus Replication / drug effects
Reg. No./Substance:
0/Immediate-Early Proteins; 0/Viral Proteins; 564-25-0/Doxycycline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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