EPSTEIN-BARR-VIRUS LYTIC REPLICATION IS CONTROLLED BY POSTTRANSCRIPTIONAL NEGATIVE REGULATION OF BZLF1

Regulation of the immediate-early gene BZLF1 is assumed to play a key role in triggering the lytic replication of Epstein-Barr virus (EBV). The expression of BZLF1 is regulated on multiple levels, including con trol of transcription by several positive and negative cis-acting elem ents as well as posttranslational modifications and protein-protein in teractions. Localization of BZLF1 on one strand of the genome and the latent EBNA1 transcription unit on the complementary strand suggests a regulatory mechanism via hybridization of antisense RNA. With a plasm id encoding a defective BZLF1 RNA, which could not be translated, we w ere able to induce expression of endogenous BZLF1 gene product Zta and other proteins of the lytic cycle. Our data show for the first time t hat latent replication is stabilized by negative regulation of an imme diate-early gene of the lytic cycle by a posttranscriptional mechanism . This might be a common theme of herpes simplex virus and EBV latency .