Functional interactions between the Epstein-Barr Virus BZLF1 protein and the promyelocytic leukemia protein

Abstract

The Epstein-Barr virus immediate-early protein BZLF1 (Z) has been shown to alter the cellular localization of the promyelocytic leukemia (PML) protein. PML has important implications for growth control, apoptosis, anti-viral effects and many more processes. Here we further examined the relationship between PML and the Epstein-Barr virus Z protein. We examined the effect of Z expression on PML protein levels, and the effect of increased PML protein levels on Z-mediated dispersion of PML bodies. We found that increased levels of PML protein, such as through interferon treatment, were able to suppress Z-mediated PML body dispersion. We also studied the consequences of PML dispersion by Z, by examining p21 transactivation, A20 transactivation, and MHC Class I presentation levels in Z-expressing cells. We found that, while Z-mediated dispersion of PML did not affect MHC Class I presentation, it did alter p21 and A20 expression. In addition, we found that increased levels of PML were able to prevent Z protein binding to mitotic chromosomes. Our work implies that the balance of PML and Z levels in cells may affect how each protein functions.