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Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections

Fusade-Boyer, Maxime and Dupré, Gabriel and Bessière, Pierre and Khiar, Samira and Quentin-Froignant, Charlotte and Beck, Cécile and Lecollinet, Sylvie and Rameix-Welti, Marie-Anne and Eléouët, Jean-François and Tangy, Frédéric and Lajoie Halova, Barbora and Bertagnoli, Stéphane and Vidalain, Pierre-Olivier and Gallardo, Franck and Volmer, Romain Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections. (2019) Frontiers in Immunology, 10. 1-12. ISSN 1664-3224

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Official URL: https://doi.org/10.3389/fimmu.2019.00134

Abstract

The guanabenz derivative Sephin1 has recently been proposed to increase the levels of translation initiation factor 2 (eIF2α) phosphorylation by inhibiting dephosphorylation by the protein phosphatase 1—GADD34 (PPP1R15A) complex. As phosphorylation of eIF2α by protein kinase R (PKR) is a prominent cellular antiviral pathway, we evaluated the consequences of Sephin1 treatment on virus replication. Our results provide evidence that Sephin1 downregulates replication of human respiratory syncytial virus, measles virus, human adenovirus 5 virus, human enterovirus D68, human cytomegalovirus, and rabbit myxoma virus. However, Sephin1 proved to be inactive against influenza virus, as well as against Japanese encephalitis virus. Sephin1 increased the levels of phosphorylated eIF2α in cells exposed to a PKR agonist. By contrast, in virus-infected cells, the levels of phosphorylated eIF2α did not always correlate with the inhibition of virus replication by Sephin1. This work identifies Sephin1 as an antiviral molecule in cell culture against RNA, as well as DNA viruses belonging to phylogenetically distant families.

Item Type:Article
HAL Id:hal-02276780
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:Other partners > Agence Nationale de Sécurité Sanitaire - ANSES (FRANCE)
French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Université de Toulouse > Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE)
Université de Toulouse > Institut National Polytechnique de Toulouse - INPT (FRANCE)
French research institutions > Institut National de la Recherche Agronomique - INRA (FRANCE)
French research institutions > Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE)
Other partners > Institut Pasteur (FRANCE)
Other partners > NeoVirTech (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UPS (FRANCE)
Other partners > Université de Versailles Saint-Quentin-en-Yvelines -UVSQ (FRANCE)
Other partners > Ecole Nationale Vétérinaire d'Alfort - ENVA (FRANCE)
Other partners > Assistance publique - Hôpitaux de Paris - AP-HP (FRANCE)
Other partners > Université Paris Descartes - Paris V (FRANCE)
Laboratory name:
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Deposited By: Loetitia MOYA
Deposited On:03 Sep 2019 08:18

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