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

Frontiers in Immunology
Maxime Fusade-BoyerRomain Volmer

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.

References

Feb 14, 2004·Journal of Virology·Christelle Camus-BouclainvilleFrédérique Messud-Petit
Jun 15, 2007·Nature Reviews. Molecular Cell Biology·David Ron, Peter Walter
Sep 14, 2011·Molecular & Cellular Proteomics : MCP·Anastassia V KomarovaFrédéric Tangy
Dec 1, 2009·Viruses·Bianca Dauber, Thorsten Wolff
May 9, 2014·ClinicoEconomics and Outcomes Research : CEOR·Tiffany L TurnerRohan Thompson
May 20, 2014·Journal of Visualized Experiments : JoVE·Marianne Lucas-HouraniPierre-Olivier Vidalain
Sep 4, 2014·The Journal of General Virology·Daniel Marc
Oct 4, 2014·Nature Communications·Marie-Anne Rameix-WeltiJean-François Eléouët
Dec 30, 2014·Current Opinion in Cell Biology·Romain Volmer, David Ron
May 27, 2015·Veterinary Microbiology·K P DaltonF Parra
Jun 23, 2015·Cell Reports·Meng S ChoyWolfgang Peti
Sep 22, 2015·Viruses·Timothy C M LiNelson Lee
Mar 2, 2016·The Lancet Infectious Diseases·Charlotte Carina Holm-HansenThea Kølsen Fischer
Oct 4, 2016·JAMA Pediatrics·Johan Christiaan Bester
Apr 20, 2017·Nature Reviews. Microbiology·Andreas S PuschnikJan E Carette
Aug 2, 2017·Nature Structural & Molecular Biology·Marta CarraraAnne Bertolotti
Sep 25, 2017·Nature Reviews. Drug Discovery·Stefan H E KaufmannRalf Bartenschlager
Jan 4, 2018·ACS Infectious Diseases·Stanford Schor, Shirit Einav
Apr 6, 2018·The Journal of Biological Chemistry·Ana Crespillo-CasadoDavid Ron
May 31, 2018·Advances in Experimental Medicine and Biology·Joanna L MillerNicole Zitzmann

❮ Previous
Next ❯

Citations

Jul 25, 2020·Virology Journal·Yuanzhi LiuXiaoyue Chen
Oct 3, 2020·European Respiratory Review : an Official Journal of the European Respiratory Society·Giulia EmanuelliStefan J Marciniak
Nov 19, 2020·Pharmacological Reviews·Muhammad Saad YousufTheodore J Price
May 29, 2021·ACS Infectious Diseases·Sandrine Kappler-GratiasFranck Gallardo
Apr 29, 2020·ACS Central Science·Maja Köhn

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear magnetic resonance
glycosylation

Software Mentioned

AnchOR3

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

© 2022 Meta ULC. All rights reserved