title: TOE1 is an inhibitor of HIV-1 replication with cell-penetrating capability.
abstract: Target of Egr1 (TOE1) is a nuclear protein localized primarily in nucleoli and Cajal bodies that was identified as a downstream target of the immediate early gene Egr1. TOE1 displays a functional deadenylation domain and has been shown to participate in spliceosome assembly. We report here that TOE1 can function as an inhibitor of HIV-1 replication and show evidence that supports a direct interaction of TOE1 with the viral specific transactivator response element as part of the inhibitory mechanism. In addition, we show that TOE1 can be secreted by activated CD8(+) T lymphocytes and can be cleaved by the serine protease granzyme B, one of the main components of cytotoxic granules. Both full-length and cleaved TOE1 can spontaneously cross the plasma membrane and penetrate cells in culture, retaining HIV-1 inhibitory activity. Antiviral potency of TOE1 and its cell-penetrating capability have been identified to lie within a 35-amino-acid region containing the nuclear localization sequence.
authors.affiliation: Ottawa Hospital Research Institute, Program in Cancer Therapeutics, The Ottawa Hospital, Ottawa, ON, Canada K1H 8L6;
authors.forename: Sabina
authors.initials: S
authors.lastname: Sperandio
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec, QC, Canada G1V 4G2;
authors.forename: Corinne
authors.initials: C
authors.lastname: Barat
authors.affiliation: Ottawa Hospital Research Institute, Program in Cancer Therapeutics, The Ottawa Hospital, Ottawa, ON, Canada K1H 8L6;
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cabrita
authors.affiliation: Department of Chemistry, University of Ottawa, Ottawa, ON, Canada K1N 6N5;
authors.forename: Ana
authors.initials: A
authors.lastname: Gargaun
authors.affiliation: Department of Chemistry, University of Ottawa, Ottawa, ON, Canada K1N 6N5;
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Berezovski
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec, QC, Canada G1V 4G2; Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Quebec, QC, Canada G1V 0A6;
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
authors.affiliation: Ottawa Hospital Research Institute, Program in Cancer Therapeutics, The Ottawa Hospital, Ottawa, ON, Canada K1H 8L6; Cell and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 iandebelle@gmail.com.
authors.forename: Ian
authors.initials: I
authors.lastname: de Belle
mesh_terms: D057809:HEK293 Cells; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D059748:Proteolysis; D015533:Transcriptional Activation; D014779:Virus Replication / Q000502:physiology*
chemical_list: D009687:Nuclear Proteins; C474027:TOE1 protein, human
keywords: HIV-1; TOE1; cell penetrating peptide; granzyme B; replication