Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100

The Epstein–Barr virus (EBV) EBNA‐LP protein is important for EBV‐mediated B‐cell immortalization and is a potent gene‐specific coactivator of the viral transcriptional activator, EBNA2. The mechanism(s) by which EBNA‐LP functions as a coactivator remains an important question in the biology of EBV‐induced B‐cell immortalization. In this study, we found that EBNA‐LP interacts with the promyelocytic leukemia nuclear body (PML NB)‐associated protein Sp100 and displaces Sp100 and heterochromatin protein 1α (HP1α) from PML NBs. Interaction between EBNA‐LP and Sp100 was mediated through conserved region 3 in EBNA‐LP and the PML NB targeting domain in Sp100. Overexpression of Sp100 lacking the N‐terminal PML NB targeting domain, but not a mutant form of Sp100 lacking the HP1α interaction domain, was sufficient to coactivate EBNA2 in a gene‐specific manner independent of EBNA‐LP. These findings suggest that Sp100 is a major mediator of EBNA‐LP coactivation. These studies indicate that modulation of PML NB‐associated proteins may be important for establishment of latent viral infections, and also identify a convenient model system to investigate the functions of Sp100.