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The Epstein–Barr virus lytic program is controlled by the co‐operative functions of two transactivators
Author(s) -
Feederle Regina,
Kost Manuela,
Baumann Matthias,
Janz Annette,
Drouet Emmanuel,
Hammerschmidt Wolfgang,
Delecluse HenriJacques
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.12.3080
Subject(s) - bzlf1 , lytic cycle , biology , epstein–barr virus , viral entry , viral replication , dna replication , virology , gene , virus , genetics , herpesviridae , viral disease
The propagation of herpesviruses has long been viewed as a temporally regulated sequential process that results from the consecutive expression of specific viral transactivators. As a key step in this process, lytic viral DNA replication is considered as a checkpoint that controls the expression of the late structural viral genes. In a novel genetic approach, we show that both hypotheses do not hold true for the Epstein–Barr virus (EBV). The study of viral mutants of EBV in which the early genes BZLF1 and BRLF1 are deleted allowed a precise assignment of the function of these proteins. Both transactivators were absolutely essential for viral DNA replication. Both BZLF1 and BRLF1 were required for full expression of the EBV proteins expressed during the lytic program, although the respective influence of these molecules on the expression of various viral target genes varied greatly. In replication‐defective viral mutants, neither early gene expression nor DNA replication was a prerequisite for late gene expression. This work shows that BRLF1 and BZLF1 harbor distinct but complementary functions that influence all stages of viral production.