Intrinsic antiviral resistance mediated by constitutively expressed cellular 
proteins is one arm of defence against virus infection. Promyelocytic leukaemia 
nuclear bodies (PML-NBs, also known as ND10) contribute to host restriction of 
herpes simplex virus type 1 (HSV-1) replication via mechanisms that are 
counteracted by viral regulatory protein ICP0. ND10 assembly is dependent on 
PML, which comprises several different isoforms, and depletion of all PML 
isoforms decreases cellular resistance to ICP0-null mutant HSV-1. We report that 
individual expression of PML isoforms I and II partially reverses the increase 
in ICP0-null mutant HSV-1 plaque formation that occurs in PML-depleted cells. 
This activity of PML isoform I is dependent on SUMO modification, its SUMO 
interaction motif (SIM), and each element of its TRIM domain. Detailed analysis 
revealed that the punctate foci formed by individual PML isoforms differ subtly 
from normal ND10 in terms of composition and/or Sp100 modification. 
Surprisingly, deletion of the SIM motif from PML isoform I resulted in increased 
colocalisation with other major ND10 components in cells lacking endogenous PML. 
Our observations suggest that complete functionality of PML is dependent on 
isoform-specific C-terminal sequences acting in concert.