The small nuclear structures known as ND10 or PML nuclear bodies have been 
implicated in a variety of cellular processes including response to stress and 
interferons, oncogenesis, and viral infection, but little is known about their 
biochemical properties. Recently, a ubiquitin-specific protease enzyme (named 
HAUSP) and a ubiquitin-homology family protein (PIC1) have been found associated 
with ND10. HAUSP binds strongly to Vmw110, a herpesvirus regulatory protein 
which has the ability to disrupt ND10, while PIC1 was identified as a protein 
which interacts with PML, the prototype ND10 protein. We have investigated the 
role of ubiquitin-related pathways in the mechanism of ND10 disruption by Vmw110 
and the effect of virus infection on PML stability. The results show that the 
disruption of ND10 during virus infection correlates with the loss of several 
PML isoforms and this process is dependent on active proteasomes. The PML 
isoforms that are most sensitive to virus infection correspond closely to those 
which have recently been identified as being covalently conjugated to PIC1. In 
addition, a large number of PIC1-protein conjugates can be detected following 
transfection of a PIC1 expression plasmid, and many of these are also eliminated 
in a Vmw110-dependent manner during virus infection. These observations provide 
a biochemical mechanism to explain the observed effects of Vmw110 on ND10 and 
suggest a simple yet powerful mechanism by which Vmw110 might function during 
virus infection.