RESISTANCE TO VIRUS-INFECTION CONFERRED BY THE INTERFERON-INDUCED PROMYELOCYTIC LEUKEMIA PROTEIN

The interferon (IFN)-induced promyelocytic leukemia (PML) protein is s pecifically associated with nuclear bodies (NBs) whose functions are y et unknown. Two of the NB-associated proteins, PML and Sp100, are indu ced by IFN. Here we show that overexpression of PML and not Sp100 indu ces resistance to infections by vesicular stomatitis virus (VSV) (a rh abdovirus) and influenza A virus (an orthomyxovirus) but not by enceph alomyocarditis virus (a picornavirus). Inhibition of viral multiplicat ion was dependent on both the level of PML expression and the multipli city of infection and reached 100-fold. PML,Fas shown to interfere wit h VSV mRNA and protein synthesis, Compared to the IFN mediator MxA pro tein, PML had less powerful antiviral activity. While nuclear body loc alization of PML did not seem to be required for the antiviral effect, deletion of the PML coiled-coil domain completely abolished it. Taken together, these results suggest that PML can contribute to the antivi ral state induced in IFN-treated cells.