Role and fate of PML nuclear bodies in response to interferon and viral infections

Interferons (IFNs) are a family of secreted proteins with antiviral, antipr oliferative and immunomodulatory activities. The different biological actio ns of IFN are believed to be mediated by the products of specifically induc ed cellular genes in the target cells. The promyelocytic leukaemia (PML) pr otein localizes both in the nucleoplasm and in matrix-associated multi-prot ein complexes known as nuclear bodies (NBs). PML is essential for the prope r formation and the integrity of the NBs. Modification of PML by the Small Ubiquitin MOdifier (SUMO) was shown to be required for its localization in NBs. The number and the intensity of PML NBs increase in response to interf eron (IFN). Inactivation of the IFN-induced PML gene by its fusion to retin oic acid receptor alpha alters the normal localization of PML from the punc tuate nuclear patterns of NBs to microdispersed tiny dots and results in un controlled growth in Acute Promyelocytic Leukaemia. The NBs-associated prot eins, PML, Sp100, Sp140, Sp110, ISG20 and PA28 are induced by IFN suggestin g that nuclear bodies could play a role in IFN response. Although the funct ion of PML NBs is still unclear, some results indicate that they may repres ent preferential targets for viral infections and that PML could play a rol e in the mechanism of the antiviral action of IFNs. Viruses, which require the cellular machinery for their replication, have evolved different ways t o counteract the action of IFN by inhibiting IFN signalling, by blocking th e activities of specific antiviral mediators or by altering PML expression and/or localization on nuclear bodies.