Early events in Epstein-Barr virus genome expression after activation: regulation by second messengers of B cell activation.
RNA transcription from the BamHI Z and BamHI R and HindIII G regions of the Epstein-Barr virus (EBV) genome was studied after treatment of Akata cells with anti-immunoglobulin G (IgG), with second messenger agonists or antagonists to determine how latent EBV activation is regulated by B cell second messengers. Northern gel analysis demonstrated that BZLF1, BZLF1 + BRLF1, and BMLF1 + BSLF2 transcripts were induced at 2 hr and increased in concentration at 4 hr after induction with anti-IgG; transcripts from BRRF1, BaRF1, BMLF1, and BMRF1 were initiated at 4 hr; a transcript from BRRF2 appeared at 6 hr. The patterns of transcription from these genes after repeated stimulations with calcium ionophore A23187 + dioctanoylglycerol paralleled those with anti-IgG except that times of initiation were delayed by about 2 hr. Nuclear run-off assay of BZLF1 gene showed rapid increases in their transcriptions from 30 to 60 min after anti-IgG treatment. The protein kinase C antagonist, staurosporine, completely blocked the appearance of these transcripts, while 8-bromo cAMP + theophylline suppressed the transcription by about 40%. The regulation of EBV activation in Akata cells with anti-IgG or with second messenger agonists or antagonists can be explained by regulation at the level of transcription of immediate-early genes of EBV.
Mellinghoff
I
I
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
Daibata
M
M
Humphreys
R E
RE
Mulder
C
C
Takada
K
K
Sairenji
T
T
D000470:Alkaloids / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000382:microbiology; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000254:growth & development; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D015290:Second Messenger Systems; D019311:Staurosporine; D013806:Theophylline / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014775:Virus Activation
D000470:Alkaloids; D000888:Antibodies, Anti-Idiotypic; D004075:Diglycerides; D007074:Immunoglobulin G; C048844:anti-IgG; C044295:1,2-dioctanoylglycerol; D000001:Calcimycin; D013806:Theophylline; D019311:Staurosporine