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The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses

Flaviviruses replicate in a wide variety of species and have a broad cellular tropism. They are isolated from various body fluids, and Zika virus (ZIKV), Japanese encephalitis virus (JEV), and West Nile virus (WNV) RNAs have been detected in nasopharyngeal swabs. Consequently, we evaluated the cellu...

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Autores principales: Vielle, Nathalie J., García-Nicolás, Obdulio, Oliveira Esteves, Blandina I., Brügger, Melanie, Summerfield, Artur, Alves, Marco P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477545/
https://www.ncbi.nlm.nih.gov/pubmed/31057517
http://dx.doi.org/10.3389/fmicb.2019.00811
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author Vielle, Nathalie J.
García-Nicolás, Obdulio
Oliveira Esteves, Blandina I.
Brügger, Melanie
Summerfield, Artur
Alves, Marco P.
author_facet Vielle, Nathalie J.
García-Nicolás, Obdulio
Oliveira Esteves, Blandina I.
Brügger, Melanie
Summerfield, Artur
Alves, Marco P.
author_sort Vielle, Nathalie J.
collection PubMed
description Flaviviruses replicate in a wide variety of species and have a broad cellular tropism. They are isolated from various body fluids, and Zika virus (ZIKV), Japanese encephalitis virus (JEV), and West Nile virus (WNV) RNAs have been detected in nasopharyngeal swabs. Consequently, we evaluated the cellular tropism and host responses upon ZIKV, JEV, WNV, and Usutu virus (USUV) infection using a relevant model of the human upper respiratory tract epithelium based on primary human nasal epithelial cells (NECs) cultured at the air-liquid interface. NECs were susceptible to all the viruses tested, and confocal analysis showed evidence of infection of ciliated and non-ciliated cells. Each flavivirus productively infected NECs, leading to apical and basolateral live virus shedding with particularly high basal release for JEV and WNV. As demonstrated by a paracellular permeability assay, the integrity of the epithelium was not affected by flavivirus infection, suggesting an active release of live virus through the basolateral surface. Also, we detected a significant secretion of interferon type III and the pro-inflammatory cytokine IP-10/CXCL10 upon infection with JEV. Taken together, our data suggest that the human upper respiratory tract epithelium is a target for flaviviruses and could potentially play a role in the spread of infection to other body compartments through basolateral virus release. Undoubtedly, further work is required to evaluate the risks and define the adapted measures to protect individuals exposed to flavivirus-contaminated body fluids.
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spelling pubmed-64775452019-05-03 The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses Vielle, Nathalie J. García-Nicolás, Obdulio Oliveira Esteves, Blandina I. Brügger, Melanie Summerfield, Artur Alves, Marco P. Front Microbiol Microbiology Flaviviruses replicate in a wide variety of species and have a broad cellular tropism. They are isolated from various body fluids, and Zika virus (ZIKV), Japanese encephalitis virus (JEV), and West Nile virus (WNV) RNAs have been detected in nasopharyngeal swabs. Consequently, we evaluated the cellular tropism and host responses upon ZIKV, JEV, WNV, and Usutu virus (USUV) infection using a relevant model of the human upper respiratory tract epithelium based on primary human nasal epithelial cells (NECs) cultured at the air-liquid interface. NECs were susceptible to all the viruses tested, and confocal analysis showed evidence of infection of ciliated and non-ciliated cells. Each flavivirus productively infected NECs, leading to apical and basolateral live virus shedding with particularly high basal release for JEV and WNV. As demonstrated by a paracellular permeability assay, the integrity of the epithelium was not affected by flavivirus infection, suggesting an active release of live virus through the basolateral surface. Also, we detected a significant secretion of interferon type III and the pro-inflammatory cytokine IP-10/CXCL10 upon infection with JEV. Taken together, our data suggest that the human upper respiratory tract epithelium is a target for flaviviruses and could potentially play a role in the spread of infection to other body compartments through basolateral virus release. Undoubtedly, further work is required to evaluate the risks and define the adapted measures to protect individuals exposed to flavivirus-contaminated body fluids. Frontiers Media S.A. 2019-04-16 /pmc/articles/PMC6477545/ /pubmed/31057517 http://dx.doi.org/10.3389/fmicb.2019.00811 Text en Copyright © 2019 Vielle, García-Nicolás, Oliveira Esteves, Brügger, Summerfield and Alves. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Vielle, Nathalie J.
García-Nicolás, Obdulio
Oliveira Esteves, Blandina I.
Brügger, Melanie
Summerfield, Artur
Alves, Marco P.
The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses
title The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses
title_full The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses
title_fullStr The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses
title_full_unstemmed The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses
title_short The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses
title_sort human upper respiratory tract epithelium is susceptible to flaviviruses
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477545/
https://www.ncbi.nlm.nih.gov/pubmed/31057517
http://dx.doi.org/10.3389/fmicb.2019.00811
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