TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus

• Published in: Journal of general virology 2009-03, Vol.90 (3), p.536-545
• Main Authors: Eldin, Patrick, Papon, Laura, Oteiza, Alexandra, Brocchi, Emiliana, Lawson, T. Glen, Mechti, Nadir
• Format: Article
• Language: English
• Subjects: 3C Viral Proteases; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Biological and medical sciences; Cell Line; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Encephalomyocarditis virus; Encephalomyocarditis virus - drug effects; Encephalomyocarditis virus - enzymology; Encephalomyocarditis virus - genetics; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Life Sciences; Microbiology; Microbiology and Parasitology; Minor Histocompatibility Antigens; Miscellaneous; Repressor Proteins - genetics; Repressor Proteins - metabolism; Repressor Proteins - pharmacology; Tripartite Motif Proteins; Ubiquitin - metabolism; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ubiquitin-Protein Ligases - pharmacology; Viral Proteins - genetics; Viral Proteins - metabolism; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.006288-0

1 Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), Montpellier, France 2 CNRS, UMR 5236, CPBS, 4 Bd Henri IV, CS 69033, F-34965 Montpellier, France 3 Université Montpellier 2, CPBS, F-34095 Montpellier, France 4 Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia, Via A. Bianchi 7, 25124 Brescia, Italy 5 Department of Chemistry, Bates College, Lewiston, ME 04240, USA Correspondence Patrick Eldin patrick.eldin{at}univ-montp1.fr The interferon (IFN) system is a major effector of the innate immunity that allows time for the subsequent establishment of an adaptive immune response against a wide-range of pathogens. Their diverse biological actions are thought to be mediated by the products of specific but usually overlapping sets of cellular genes induced in the target cells. Ubiquitin ligase members of the tripartite motif (TRIM) protein family have emerged as IFN-induced proteins involved in both innate and adaptive immunity. In this report, we provide evidence that TRIM22 is a functional E3 ubiquitin ligase that is also ubiquitinated itself. We demonstrate that TRIM22 expression leads to a viral protection of HeLa cells against encephalomyocarditis virus infections. This effect is dependent upon its E3 ubiquitinating activity, since no antiviral effect was observed in cells expressing a TRIM22-deletion mutant defective in ubiquitinating activity. Consistent with this, TRIM22 interacts with the viral 3C protease (3C PRO ) and mediates its ubiquitination. Altogether, our findings demonstrate that TRIM22 E3 ubiquitin ligase activity represents a new antiviral pathway induced by IFN against picornaviruses. Published online ahead of print on 27 November 2008 as DOI 10.1099/vir.0.006288-0.