Related Experiment Videos
Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein
M K Chelbi-Alix1, F Quignon, L Pelicano
1CNRS UPR 9051, Centre Hayem, Hôpital St. Louis, Paris, France. mchelbi@infobiogen.fr
Abstract:
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.
Insights
The promyelocytic leukemia (PML) protein, induced by interferon, provides resistance against certain viral infections by interfering with viral synthesis. PML
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Interferon (IFN) treatment induces cellular antiviral states.
- Promyelocytic leukemia (PML) protein localizes to nuclear bodies (NBs).
- The function of NBs and the role of PML in antiviral defense are largely unknown.
Purpose of the Study:
- To investigate the antiviral potential of the PML protein.
- To determine if PML contributes to the interferon-induced antiviral state.
Main Methods:
- Overexpression of PML and Sp100 proteins in cells.
- Infection assays using vesicular stomatitis virus (VSV), influenza A virus, and encephalomyocarditis virus (EMCV).
- Analysis of viral mRNA and protein synthesis.
- Site-directed mutagenesis of the PML protein (coiled-coil domain deletion).
Main Results:
- PML overexpression conferred resistance to VSV and influenza A virus, but not EMCV.
- Antiviral effect was dependent on PML expression levels and viral multiplicity of infection, reaching up to 100-fold inhibition.
- PML interfered with VSV mRNA and protein synthesis.
- Deletion of the PML coiled-coil domain abolished antiviral activity, while NB localization was not essential.
- PML's antiviral activity was less potent than the IFN-mediator MxA protein.
Conclusions:
- PML protein possesses antiviral activity against specific RNA viruses.
- PML contributes to the antiviral state induced by interferon.
- The coiled-coil domain of PML is critical for its antiviral function.