Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782340641673445376 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4204995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT maroisisabelle inhibitionofinfluenzavirusreplicationbytargetingbroadhostcellpathways AT cloutieralexandre inhibitionofinfluenzavirusreplicationbytargetingbroadhostcellpathways AT meunierisabelle inhibitionofinfluenzavirusreplicationbytargetingbroadhostcellpathways AT weingartlhanam inhibitionofinfluenzavirusreplicationbytargetingbroadhostcellpathways AT cantinandrem inhibitionofinfluenzavirusreplicationbytargetingbroadhostcellpathways AT richtermartinv inhibitionofinfluenzavirusreplicationbytargetingbroadhostcellpathways |