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Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections
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 c...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379315/ https://www.ncbi.nlm.nih.gov/pubmed/30809223 http://dx.doi.org/10.3389/fimmu.2019.00134 |
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author | Fusade-Boyer, Maxime Dupré, Gabriel Bessière, Pierre Khiar, Samira Quentin-Froignant, Charlotte Beck, Cécile Lecollinet, Sylvie Rameix-Welti, Marie-Anne Eléouët, Jean-François Tangy, Frédéric Lajoie, Barbora Bertagnoli, Stéphane Vidalain, Pierre-Olivier Gallardo, Franck Volmer, Romain |
author_facet | Fusade-Boyer, Maxime Dupré, Gabriel Bessière, Pierre Khiar, Samira Quentin-Froignant, Charlotte Beck, Cécile Lecollinet, Sylvie Rameix-Welti, Marie-Anne Eléouët, Jean-François Tangy, Frédéric Lajoie, Barbora Bertagnoli, Stéphane Vidalain, Pierre-Olivier Gallardo, Franck Volmer, Romain |
author_sort | Fusade-Boyer, Maxime |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6379315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63793152019-02-26 Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections Fusade-Boyer, Maxime Dupré, Gabriel Bessière, Pierre Khiar, Samira Quentin-Froignant, Charlotte Beck, Cécile Lecollinet, Sylvie Rameix-Welti, Marie-Anne Eléouët, Jean-François Tangy, Frédéric Lajoie, Barbora Bertagnoli, Stéphane Vidalain, Pierre-Olivier Gallardo, Franck Volmer, Romain Front Immunol Immunology 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. Frontiers Media S.A. 2019-02-12 /pmc/articles/PMC6379315/ /pubmed/30809223 http://dx.doi.org/10.3389/fimmu.2019.00134 Text en Copyright © 2019 Fusade-Boyer, Dupré, Bessière, Khiar, Quentin-Froignant, Beck, Lecollinet, Rameix-Welti, Eléouët, Tangy, Lajoie, Bertagnoli, Vidalain, Gallardo and Volmer. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Fusade-Boyer, Maxime Dupré, Gabriel Bessière, Pierre Khiar, Samira Quentin-Froignant, Charlotte Beck, Cécile Lecollinet, Sylvie Rameix-Welti, Marie-Anne Eléouët, Jean-François Tangy, Frédéric Lajoie, Barbora Bertagnoli, Stéphane Vidalain, Pierre-Olivier Gallardo, Franck Volmer, Romain Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections |
title | Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections |
title_full | Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections |
title_fullStr | Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections |
title_full_unstemmed | Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections |
title_short | Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections |
title_sort | evaluation of the antiviral activity of sephin1 treatment and its consequences on eif2α phosphorylation in response to viral infections |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379315/ https://www.ncbi.nlm.nih.gov/pubmed/30809223 http://dx.doi.org/10.3389/fimmu.2019.00134 |
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