THE ACUTE PROMYELOCYTIC LEUKEMIA-ASSOCIATED PML GENE IS INDUCED BY INTERFERON

The PML protein concentrates within discrete nuclear structures known as nuclear bodies, also called NDs or PODs, which contain several prot eins including the interferon (IFN)-inducible SP100 product, The funct ion of these structures remains elusive, We and others have shown rece ntly that they represent specific targets for adenovirus and herpes si mplex virus. This prompted us to investigate whether PML, like SP100, might be induced by IFN and to explore the role of PML in viral infect ion, Here we report that PML mRNA levels increase rapidly in response to interferon treatment, This accumulation of. PML transcripts is a pr imary IFN response since it does not require de novo protein synthesis , The IFN-induced activation of the PML gene is accompanied by enhance d protein expression as revealed by immunolabelling, Both the intensit y of the staining and the number of labelled structures increased upon interferon exposure, To probe the role of PML in IFN action, we compa red the antiviral state established by alpha-interferon in embryonic f ibroblasts (EFs) derived from null mutant mice for PML and from wild-t ype control mice, The resistance to viral infection conferred by IFN-a lpha was identical in both PML(+/+) and PML(m/m) fibroblasts indicatin g that PML is not an essential mediator of the antiviral effect of int erferon, We also noted that DNA-binding factors are normally activated by IFN in PML(m/m) cells.