SEQUESTRATION OF PML AND SP100 PROTEINS IN AN INTRANUCLEAR VIRAL STRUCTURE DURING HERPES-SIMPLEX VIRUS TYPE-1 INFECTION

We investigated the intranuclear distribution of PML and Sp100 in HeLa cells at the ultrastructural level and examined their relocalization in response to herpes simplex virus type 1 (HSV-1) infection. In the a bsence of infection, we observed that both are components, not only of nuclear bodies, but also of interchromatin granule-associated zones, which suggests a potential role for PML and Sp100 in splicing events. Prolonged HSV-I infection induced dramatic changes in nuclear organiza tion which consisted of the morphological disappearance of some nuclea r structures (nuclear bodies, interchromatin granule associated zones, coiled bodies) and of the development of a centrally located electron -translucent viral region which pushed the cellular clusters of interc hromatin gran ules to the nuclear border. Concomitantly, dense bodies, concentric arrays of reduplicated inner nuclear membrane, and translu cent patches containing a few viral capsids occurred at the nuclear bo rder. PML and Sp100 were exclusively detected over the finely granular material of the viral translucent patches which also contains small a mounts of p80-coilin and U1 and U2 snRNAs. An antiserum raised against capsid proteins intensely labeled the viral translucent patches at th e level of their finely granular material and enclosed viral capsids. Our data, therefore, suggest that these viral structures, in addition to being the site of accumulation of viral capsid proteins and, possib ly, a capsid-works, are also a site of sequestration of cell factors i ncluding PML and Sp100. Viral capsid proteins could interfere with and inactivate PML and Sp100 and be implicated in the shutoff of host cel l metabolism induced by HSV-1 infection. (C) 1995 Academic Press, Inc.