Effects of SUMO-1 upon Epstein-Barr virus BZLF1 function and BMRF1 expression

Epstein-Barr virus (EBV) is a human herpesvirus that has infected at least 90% of the world population. This very successful virus causes infectious mononucleosis and is associated with many different types of cancer. The EBV BZLF1 protein is a transcription factor that has also been shown to interact with many host cell proteins and pathways. BZLF1 (Z) is tagged by the small ubiquitin-related modifier-1 (SUMO-1) protein. Here, we present studies of the functional consequences of SUMO-1 modification of Z. We found that SUMO-1 modification of Z has no apparent effect upon the stability and localization of the Z protein. We did find, however, that SUMO-1 modification decreases the transactivation activity of Z on specific promoters. In addition, when SUMO-1 is supplied to cells when lytic replication is induced, EBV BMRF1 levels greatly increase, suggesting that SUMO-1 enhances EBV lytic replication. Therefore, SUMO-1 modification of proteins appears to have an important role in EBV lytic replication.