Al. Adamson et S. Kenney, Epstein-Barr virus immediate-early protein BZLF1 is SUMO-1 modified and disrupts promyelocytic leukemia bodies, J VIROLOGY, 75(5), 2001, pp. 2388-2399
Although the immediate-early proteins of both herpes simplex virus (HSV) an
d cytomegalovirus (CMV) are known to modify promyelocytic leukemia (PML) (N
D10) bodies in the nucleus of the host cell, it has been unclear whether ly
tic infection with gamma herpesviruses induces a similar effect. The PML pr
otein is induced by interferon, involved in major histocompatibility comple
x class I presentation, and necessary for certain types of apoptosis. There
fore, it is likely that PML bodies function in an antiviral capacity. SUMO-
1 modification of PML is known to be required for the formation of PML bodi
es, To examine whether Epstein-Barr virus (EBV) lytic replication interfere
s with PML bodies, we expressed the EBV immediate-early genes BZLF1 (Z) and
BRLF1 (R) in EBV-positive cell lines and examined PML localization. Both Z
and R expression resulted in PML dispersion in EBV-positive cells. Z but n
ot R expression is sufficient to disrupt PML bodies in EBV-negative cell li
nes. We show that dispersion of PML bodies by Z requires a portion of the t
ranscriptional activation domain of Z but not the DNA-binding function. As
was previously reported for the HSV-1 ICP0 and CMV IE1 proteins, Z reduces
the amount of SUMO-l-modified PML. We also found that Z itself is SUMO-1 mo
dified (through amino acid 12) and that Z competes with PML for limiting am
ounts of SUMO-1. These results suggest that disruption of PML bodies is imp
ortant for efficient lytic replication of EBV. Furthermore, Z may potential
ly alter the function of a variety of cellular proteins by inhibiting SUMO-
1 modification.