Evaluation of the Antiviral Activity of Sephin1 Treatment and Its Consequences on eIF2α Phosphorylation in Response to Viral Infections
Year: 2019
Type: article
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.
Source: Frontiers in Immunology
Institutions: École Nationale Vétérinaire de Toulouse, Interactions hôtes-agents pathogènes, Institut National de la Recherche Agronomique, Université de Toulouse, Centre National de la Recherche Scientifique, Institut Pasteur, Department of Virology, Institut des Technologies Avancées en sciences du Vivant, École Nationale Vétérinaire d'Alfort, Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, Virologie, Inserm, Université de Versailles Saint-Quentin-en-Yvelines, Assistance Publique – Hôpitaux de Paris, Hôpital Ambroise-Paré, Infection et inflammation, Université Paris-Saclay, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Virologie et Immunologie Moléculaires, Université Toulouse III - Paul Sabatier, Institut National Polytechnique de Toulouse, Laboratoire de Génie Chimique, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funder: Université de Genève
OpenAlex ID: W2912936249