title: TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus.
abstract: 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.
authors.affiliation: Université Montpellier 2, CPBS, F-34095 Montpellier, France.|CNRS, UMR 5236, CPBS, 4 Bd Henri IV, CS 69033, F-34965 Montpellier, France.|Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), Montpellier, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Eldin
authors.affiliation: Université Montpellier 2, CPBS, F-34095 Montpellier, France.|CNRS, UMR 5236, CPBS, 4 Bd Henri IV, CS 69033, F-34965 Montpellier, France.|Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), Montpellier, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Papon
authors.affiliation: Université Montpellier 2, CPBS, F-34095 Montpellier, France.|CNRS, UMR 5236, CPBS, 4 Bd Henri IV, CS 69033, F-34965 Montpellier, France.|Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), Montpellier, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Oteiza
authors.affiliation: Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia, Via A. Bianchi 7, 25124 Brescia, Italy.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Brocchi
authors.affiliation: Department of Chemistry, Bates College, Lewiston, ME 04240, USA.
authors.forename: T Glen
authors.initials: TG
authors.lastname: Lawson
authors.affiliation: Université Montpellier 2, CPBS, F-34095 Montpellier, France.|CNRS, UMR 5236, CPBS, 4 Bd Henri IV, CS 69033, F-34965 Montpellier, France.|Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), Montpellier, France.
authors.forename: Nadir
authors.initials: N
authors.lastname: Mechti
mesh_terms: D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004686:Encephalomyocarditis virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C094314:TRIM22 protein, human; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases