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Inhibition of Influenza Virus Replication by Targeting Broad Host Cell Pathways

Antivirals that are currently used to treat influenza virus infections target components of the virus which can mutate rapidly. Consequently, there has been an increase in the number of resistant strains to one or many antivirals in recent years. Here we compared the antiviral effects of lysosomotro...

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Autores principales: Marois, Isabelle, Cloutier, Alexandre, Meunier, Isabelle, Weingartl, Hana M., Cantin, André M., Richter, Martin V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204995/
https://www.ncbi.nlm.nih.gov/pubmed/25333287
http://dx.doi.org/10.1371/journal.pone.0110631
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author Marois, Isabelle
Cloutier, Alexandre
Meunier, Isabelle
Weingartl, Hana M.
Cantin, André M.
Richter, Martin V.
author_facet Marois, Isabelle
Cloutier, Alexandre
Meunier, Isabelle
Weingartl, Hana M.
Cantin, André M.
Richter, Martin V.
author_sort Marois, Isabelle
collection PubMed
description Antivirals that are currently used to treat influenza virus infections target components of the virus which can mutate rapidly. Consequently, there has been an increase in the number of resistant strains to one or many antivirals in recent years. Here we compared the antiviral effects of lysosomotropic alkalinizing agents (LAAs) and calcium modulators (CMs), which interfere with crucial events in the influenza virus replication cycle, against avian, swine, and human viruses of different subtypes in MDCK cells. We observed that treatment with LAAs, CMs, or a combination of both, significantly inhibited viral replication. Moreover, the drugs were effective even when they were administered 8 h after infection. Finally, analysis of the expression of viral acidic polymerase (PA) revealed that both drugs classes interfered with early events in the viral replication cycle. This study demonstrates that targeting broad host cellular pathways can be an efficient strategy to inhibit influenza replication. Furthermore, it provides an interesting avenue for drug development where resistance by the virus might be reduced since the virus is not targeted directly.
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spelling pubmed-42049952014-10-27 Inhibition of Influenza Virus Replication by Targeting Broad Host Cell Pathways Marois, Isabelle Cloutier, Alexandre Meunier, Isabelle Weingartl, Hana M. Cantin, André M. Richter, Martin V. PLoS One Research Article Antivirals that are currently used to treat influenza virus infections target components of the virus which can mutate rapidly. Consequently, there has been an increase in the number of resistant strains to one or many antivirals in recent years. Here we compared the antiviral effects of lysosomotropic alkalinizing agents (LAAs) and calcium modulators (CMs), which interfere with crucial events in the influenza virus replication cycle, against avian, swine, and human viruses of different subtypes in MDCK cells. We observed that treatment with LAAs, CMs, or a combination of both, significantly inhibited viral replication. Moreover, the drugs were effective even when they were administered 8 h after infection. Finally, analysis of the expression of viral acidic polymerase (PA) revealed that both drugs classes interfered with early events in the viral replication cycle. This study demonstrates that targeting broad host cellular pathways can be an efficient strategy to inhibit influenza replication. Furthermore, it provides an interesting avenue for drug development where resistance by the virus might be reduced since the virus is not targeted directly. Public Library of Science 2014-10-21 /pmc/articles/PMC4204995/ /pubmed/25333287 http://dx.doi.org/10.1371/journal.pone.0110631 Text en © 2014 Marois et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Marois, Isabelle
Cloutier, Alexandre
Meunier, Isabelle
Weingartl, Hana M.
Cantin, André M.
Richter, Martin V.
Inhibition of Influenza Virus Replication by Targeting Broad Host Cell Pathways
title Inhibition of Influenza Virus Replication by Targeting Broad Host Cell Pathways
title_full Inhibition of Influenza Virus Replication by Targeting Broad Host Cell Pathways
title_fullStr Inhibition of Influenza Virus Replication by Targeting Broad Host Cell Pathways
title_full_unstemmed Inhibition of Influenza Virus Replication by Targeting Broad Host Cell Pathways
title_short Inhibition of Influenza Virus Replication by Targeting Broad Host Cell Pathways
title_sort inhibition of influenza virus replication by targeting broad host cell pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204995/
https://www.ncbi.nlm.nih.gov/pubmed/25333287
http://dx.doi.org/10.1371/journal.pone.0110631
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