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Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection

Zika virus (ZIKV) is a highly transmissive virus that belongs to the Flaviviridae family, which comprises several other pathogens that threaten human health. This re-emerging virus gained attention during the outbreak in Brazil in 2016, where a considerable number of microcephaly cases in newborns w...

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Autores principales: Sabino, Catarina, Basic, Michael, Bender, Daniela, Elgner, Fabian, Himmelsbach, Kiyoshi, Hildt, Eberhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630673/
https://www.ncbi.nlm.nih.gov/pubmed/31174294
http://dx.doi.org/10.3390/v11060524
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author Sabino, Catarina
Basic, Michael
Bender, Daniela
Elgner, Fabian
Himmelsbach, Kiyoshi
Hildt, Eberhard
author_facet Sabino, Catarina
Basic, Michael
Bender, Daniela
Elgner, Fabian
Himmelsbach, Kiyoshi
Hildt, Eberhard
author_sort Sabino, Catarina
collection PubMed
description Zika virus (ZIKV) is a highly transmissive virus that belongs to the Flaviviridae family, which comprises several other pathogens that threaten human health. This re-emerging virus gained attention during the outbreak in Brazil in 2016, where a considerable number of microcephaly cases in newborns was associated with ZIKV infection during pregnancy. Lacking a preventive vaccine or antiviral drugs, efforts have been made to better understand the viral life cycle. In light of this, the relevance of the endosomal–lysosomal compartment for the ZIKV life cycle was investigated. A549 and SH-SY5Y cells were infected with either the African strain (associated with mild symptoms) or the French Polynesia strain (associated with neurological complications). For both strains, the V-ATPase inhibitor, bafilomycin A1, efficiently inhibited ZIKV entry and prevented the spread of the infection by interfering with viral maturation. Additionally, affecting cholesterol metabolism and transport with the drug U18666A, which inactivates late endosomes and lysosomes, impairs the viral life cycle. The data presented show a clear antiviral effect of two compounds that target the same compartments in different ways. This highlights the relevance of the endosomal–lysosomal compartment for the viral life cycle that should be considered as a target for antivirals.
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spelling pubmed-66306732019-08-19 Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection Sabino, Catarina Basic, Michael Bender, Daniela Elgner, Fabian Himmelsbach, Kiyoshi Hildt, Eberhard Viruses Article Zika virus (ZIKV) is a highly transmissive virus that belongs to the Flaviviridae family, which comprises several other pathogens that threaten human health. This re-emerging virus gained attention during the outbreak in Brazil in 2016, where a considerable number of microcephaly cases in newborns was associated with ZIKV infection during pregnancy. Lacking a preventive vaccine or antiviral drugs, efforts have been made to better understand the viral life cycle. In light of this, the relevance of the endosomal–lysosomal compartment for the ZIKV life cycle was investigated. A549 and SH-SY5Y cells were infected with either the African strain (associated with mild symptoms) or the French Polynesia strain (associated with neurological complications). For both strains, the V-ATPase inhibitor, bafilomycin A1, efficiently inhibited ZIKV entry and prevented the spread of the infection by interfering with viral maturation. Additionally, affecting cholesterol metabolism and transport with the drug U18666A, which inactivates late endosomes and lysosomes, impairs the viral life cycle. The data presented show a clear antiviral effect of two compounds that target the same compartments in different ways. This highlights the relevance of the endosomal–lysosomal compartment for the viral life cycle that should be considered as a target for antivirals. MDPI 2019-06-06 /pmc/articles/PMC6630673/ /pubmed/31174294 http://dx.doi.org/10.3390/v11060524 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sabino, Catarina
Basic, Michael
Bender, Daniela
Elgner, Fabian
Himmelsbach, Kiyoshi
Hildt, Eberhard
Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection
title Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection
title_full Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection
title_fullStr Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection
title_full_unstemmed Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection
title_short Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection
title_sort bafilomycin a1 and u18666a efficiently impair zikv infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630673/
https://www.ncbi.nlm.nih.gov/pubmed/31174294
http://dx.doi.org/10.3390/v11060524
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