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Journal of Virology, September 2006, p. 8582-8592, Vol. 80, No. 17
0022-538X/06/$08.00+0 doi:10.1128/JVI.00031-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Cross Talk between PML and p53 during Poliovirus Infection: Implications for Antiviral Defense
Mathieu Pampin,1
Yannick Simonin,2
Bruno Blondel,2
Yann Percherancier,1 and
Mounira K. Chelbi-Alix1*
CNRS FRE 2944, Institut Lwoff, 7 rue Guy Moquet, 94801 Villejuif, France,1
Institut Pasteur, 75724 Paris, France2
Received 4 January 2006/
Accepted 12 June 2006
PML nuclear bodies (NBs) are dynamic intranuclear structures harboring numerous transiently or permanently localized proteins. PML, the NBs' organizer, is directly induced by interferon, and its expression is critical for antiviral host defense. We describe herein the molecular events following poliovirus infection that lead to PML-dependent p53 activation and protection against virus infection. Poliovirus infection induces PML phosphorylation through the extracellular signal-regulated kinase pathway, increases PML SUMOylation, and induces its transfer from the nucleoplasm to the nuclear matrix. These events result in the recruitment of p53 to PML NBs, p53 phosphorylation on Ser15, and activation of p53 target genes leading to the induction of apoptosis. Moreover, the knock-down of p53 by small interfering RNA results in higher poliovirus replication, suggesting that p53 participates in antiviral defense. This effect, which requires the presence of PML, is transient since poliovirus targets p53 by inducing its degradation in a proteasome- and MDM2-dependent manner. Our results provide evidence of how poliovirus counteracts p53 antiviral activity by regulating PML and NBs, thus leading to p53 degradation.
* Corresponding author. Mailing address: CNRS FRE 2944, Institut Lwoff, 7 rue Guy Moquet, Villejuif 94801, France. Phone: 33 1 49 58 33 51. Fax: 33 1 49 58 33 48. E-mail:
mchelbi{at}vjf.cnrs.fr.
Journal of Virology, September 2006, p. 8582-8592, Vol. 80, No. 17
0022-538X/06/$08.00+0 doi:10.1128/JVI.00031-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
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