Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein.
The interferon (IFN)-induced promyelocytic leukemia (PML) protein is specifically associated with nuclear bodies (NBs) whose functions are yet unknown. Two of the NB-associated proteins, PML and Sp100, are induced by IFN. Here we show that overexpression of PML and not Sp100 induces resistance to infections by vesicular stomatitis virus (VSV) (a rhabdovirus) and influenza A virus (an orthomyxovirus) but not by encephalomyocarditis virus (a picornavirus). Inhibition of viral multiplication was dependent on both the level of PML expression and the multiplicity of infection and reached 100-fold. PML was shown to interfere with VSV mRNA and protein synthesis. Compared to the IFN mediator MxA protein, PML had less powerful antiviral activity. While nuclear body localization 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 antiviral state induced in IFN-treated cells.
Chelbi-Alix
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MK
CNRS UPR 9051, Centre Hayem, Hôpital St. Louis, Paris, France. mchelbi@infobiogen.fr
Quignon
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Pelicano
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Koken
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de Thé
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D000818:Animals; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D004198:Disease Susceptibility; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human / Q000378:metabolism*; D007372:Interferons / Q000494:pharmacology*; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D018353:Rhabdoviridae Infections / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014721:Vesicular stomatitis Indiana virus
D034961:Antigens, Nuclear; D001324:Autoantigens; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C066642:SP100 protein, human; C070576:PML protein, human; D007372:Interferons