Reciprocal antagonism of steroid hormones and BZLF1 in switch between Epstein-Barr virus latent and productive cycle gene expression.
BZLF1 repression of transcription from the Epstein-Barr virus BC-R2 promoter (Cp) was shown to require a glucocorticoid response element in cis and glucocorticoids in trans. The mechanism of the repression is indirect and involves up regulation of the cellular c-fos proto-oncogene. Glucocorticoids maintain Epstein-Barr virus latency, and removal of glucocorticoids from the cell culture medium results in activation of the productive cycle. This inverse regulation of the expression of latent and productive cycle genes contributes to the switch between virus latency and the productive cycle. Glucocorticoid control of BC-R2 might also provide a mechanism for EBNA promoter switching during early infection and in development of the restricted latent pattern of gene expression.
Sinclair
A J
AJ
Ludwig Institute for Cancer Research, St. Mary's Hospital Medical School, London, United Kingdom.
Brimmell
M
M
Farrell
P J
PJ
D016475:3T3 Cells; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D004279:DNA, Viral; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015536:Down-Regulation; D019309:Epstein-Barr Virus Nuclear Antigens; D015967:Gene Expression Regulation, Viral; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015534:Trans-Activators; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
D000956:Antigens, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D005938:Glucocorticoids; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012097:Repressor Proteins; D015534:Trans-Activators; D014764:Viral Proteins