PML and PML nuclear bodies: implications in antiviral defence.

The establishment of an intracellular antiviral state is the defining activity of interferons (IFNs) as well as the property that permitted their discovery. Several pathways have been implicated in resistance to viral infection in IFN-treated cells, one of which implicates the ProMyelocytic Leukaemia (PML) protein and PML nuclear bodies (NBs, also known as ND10). PML NBs are dynamic intranuclear structures that require PML for their formation and which harbour numerous other transiently or permanently localised proteins. PML is expressed as a family of isoforms (PML I-VII) as a result of alternative splicing, most of which are found in the nucleus. IFN treatment directly induces transcription of the genes encoding both PML and Sp100, (another major component of PML NBs), resulting in higher levels of expression of these proteins and increases in both the size and number of PML NBs. These and other observations have encouraged the hypothesis that PML, PML NBs and a number of other constituents of these structures are involved in host antiviral defences. For example, exogenous expression of PML III or PML VI can impede infection by a number of RNA and DNA viruses, and certain viral proteins accumulate in PML NBs then cause their disruption by a variety of mechanisms. Although there are many other functions of PML NBs in a wide range of cellular pathways, there is accumulating evidence that they represent preferential targets for viral infections and that PML plays a role in the mechanism of the antiviral action of IFN. This article reviews the potential antiviral activities of PML NB constituent proteins, how RNA and DNA viruses overcome these defences, and the connections between these events and IFN pathways.