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The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly

Zika virus (ZIKV) is a mosquito-borne virus that belongs to the Flaviviridae family, together with dengue, yellow fever, and West Nile viruses. In the wake of its emergence in the French Polynesia and in the Americas, ZIKV has been shown to cause congenital microcephaly. It is the first arbovirus wh...

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Autores principales: Alfano, Christian, Gladwyn-Ng, Ivan, Couderc, Thérèse, Lecuit, Marc, Nguyen, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445045/
https://www.ncbi.nlm.nih.gov/pubmed/30971894
http://dx.doi.org/10.3389/fncel.2019.00094
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author Alfano, Christian
Gladwyn-Ng, Ivan
Couderc, Thérèse
Lecuit, Marc
Nguyen, Laurent
author_facet Alfano, Christian
Gladwyn-Ng, Ivan
Couderc, Thérèse
Lecuit, Marc
Nguyen, Laurent
author_sort Alfano, Christian
collection PubMed
description Zika virus (ZIKV) is a mosquito-borne virus that belongs to the Flaviviridae family, together with dengue, yellow fever, and West Nile viruses. In the wake of its emergence in the French Polynesia and in the Americas, ZIKV has been shown to cause congenital microcephaly. It is the first arbovirus which has been proven to be teratogenic and sexually transmissible. Confronted with this major public health challenge, the scientific and medical communities teamed up to precisely characterize the clinical features of congenital ZIKV syndrome and its underlying pathophysiological mechanisms. This review focuses on the critical impact of the unfolded protein response (UPR) on ZIKV-associated congenital microcephaly. ZIKV infection of cortical neuron progenitors leads to high endoplasmic reticulum (ER) stress. This results in both the stalling of indirect neurogenesis, and UPR-dependent neuronal apoptotic death, and leads to cortical microcephaly. In line with these results, the administration of molecules inhibiting UPR prevents ZIKV-induced cortical microcephaly. The discovery of the link between ZIKV infection and UPR activation has a broader relevance, since this pathway plays a crucial role in many distinct cellular processes and its induction by ZIKV may account for several reported ZIKV-associated defects.
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spelling pubmed-64450452019-04-10 The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly Alfano, Christian Gladwyn-Ng, Ivan Couderc, Thérèse Lecuit, Marc Nguyen, Laurent Front Cell Neurosci Neuroscience Zika virus (ZIKV) is a mosquito-borne virus that belongs to the Flaviviridae family, together with dengue, yellow fever, and West Nile viruses. In the wake of its emergence in the French Polynesia and in the Americas, ZIKV has been shown to cause congenital microcephaly. It is the first arbovirus which has been proven to be teratogenic and sexually transmissible. Confronted with this major public health challenge, the scientific and medical communities teamed up to precisely characterize the clinical features of congenital ZIKV syndrome and its underlying pathophysiological mechanisms. This review focuses on the critical impact of the unfolded protein response (UPR) on ZIKV-associated congenital microcephaly. ZIKV infection of cortical neuron progenitors leads to high endoplasmic reticulum (ER) stress. This results in both the stalling of indirect neurogenesis, and UPR-dependent neuronal apoptotic death, and leads to cortical microcephaly. In line with these results, the administration of molecules inhibiting UPR prevents ZIKV-induced cortical microcephaly. The discovery of the link between ZIKV infection and UPR activation has a broader relevance, since this pathway plays a crucial role in many distinct cellular processes and its induction by ZIKV may account for several reported ZIKV-associated defects. Frontiers Media S.A. 2019-03-26 /pmc/articles/PMC6445045/ /pubmed/30971894 http://dx.doi.org/10.3389/fncel.2019.00094 Text en Copyright © 2019 Alfano, Gladwyn-Ng, Couderc, Lecuit and Nguyen. 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 Neuroscience
Alfano, Christian
Gladwyn-Ng, Ivan
Couderc, Thérèse
Lecuit, Marc
Nguyen, Laurent
The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly
title The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly
title_full The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly
title_fullStr The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly
title_full_unstemmed The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly
title_short The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly
title_sort unfolded protein response: a key player in zika virus-associated congenital microcephaly
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445045/
https://www.ncbi.nlm.nih.gov/pubmed/30971894
http://dx.doi.org/10.3389/fncel.2019.00094
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