Document Detail


Stimulus duration and response time independently influence the kinetics of lytic cycle reactivation of Epstein-Barr virus.
MedLine Citation:
PMID:  19656890     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epstein-Barr virus (EBV) can be reactivated from latency into the lytic cycle by many stimuli believed to operate by different mechanisms. Cell lines containing EBV differ in their responses to inducing stimuli, yet all stimuli require de novo protein synthesis (44). A crucial step preliminary to identifying these proteins and determining when they are required is to measure the duration of stimulus and response time needed for activation of expression of EBV BRLF1 and BZLF1, the earliest viral indicators of reactivation. Here we show, with four EBV-containing cell lines that respond to different inducing agents, that stimuli that are effective at reactivating EBV can be divided into two main groups. The histone deacetylase inhibitors sodium butyrate and trichostatin A require a relatively long period of exposure, from 2 to 4 h or longer. Phorbol esters, anti-immunoglobulin G (anti-IgG), and, surprisingly, 5-aza-2'-deoxycytidine require short exposures of 15 min or less. The cell/virus background influences the response time. Expression of the EBV BZLF1 and BRLF1 genes can be detected before 2 h in Akata cells treated with anti-IgG, but both long- and short-duration stimuli required 4 or more hr to activate BZLF1 and BRLF1 expression in HH514-16, Raji, or B95-8 cells. Thus, stimulus duration and response time are independent variables. Neither stimulus duration nor response time can be predicted by the number of cells activated into the lytic cycle. These experiments shed new light on the earliest events leading to lytic cycle reactivation of EBV.
Authors:
Jill Countryman; Lyndle Gradoville; Sumita Bhaduri-McIntosh; Jianjiang Ye; Lee Heston; Sarah Himmelfarb; Duane Shedd; George Miller
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-08-05
Journal Detail:
Title:  Journal of virology     Volume:  83     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-24     Completed Date:  2009-10-16     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10694-709     Citation Subset:  IM    
Affiliation:
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Anti-Idiotypic / pharmacology*
Cell Line
Enzyme Inhibitors / pharmacology*
Herpesvirus 4, Human / metabolism,  physiology*
Histone Deacetylase Inhibitors*
Histone Deacetylases / pharmacology
Humans
Immediate-Early Proteins / genetics,  metabolism
Lymphocytes / virology*
Phorbol Esters / pharmacology*
Time Factors
Trans-Activators / genetics,  metabolism
Viral Proteins / genetics,  metabolism
Virus Activation / drug effects*
Grant Support
ID/Acronym/Agency:
CA12055/CA/NCI NIH HHS; CA16038/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Anti-Idiotypic; 0/BRLF1 protein, Human herpesvirus 4; 0/BZLF1 protein, Herpesvirus 4, Human; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Immediate-Early Proteins; 0/Phorbol Esters; 0/Trans-Activators; 0/Viral Proteins; 0/anti-IgG; EC 3.5.1.98/Histone Deacetylases
Comments/Corrections

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