Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal/Glial Cells

Tick-borne encephalitis virus (TBEV), a member of the <i>Flaviviridae</i> family, <i>Flavivirus</i> genus, is responsible for neurological symptoms that may cause permanent disability or death. With an incidence on the rise, it is the major arbovirus affecting humans in Centr...

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Autores principales: Mazigh Fares, Kamila Gorna, Noémie Berry, Marielle Cochet-Bernoin, François Piumi, Odile Blanchet, Nadia Haddad, Jennifer Richardson, Muriel Coulpier
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:5de4f915746941d6940647ff896ac8da2021-11-25T19:13:49ZTranscriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal/Glial Cells10.3390/v131122551999-4915https://doaj.org/article/5de4f915746941d6940647ff896ac8da2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2255https://doaj.org/toc/1999-4915Tick-borne encephalitis virus (TBEV), a member of the <i>Flaviviridae</i> family, <i>Flavivirus</i> genus, is responsible for neurological symptoms that may cause permanent disability or death. With an incidence on the rise, it is the major arbovirus affecting humans in Central/Northern Europe and North-Eastern Asia. Neuronal death is a critical feature of TBEV infection, yet little is known about the type of death and the molecular mechanisms involved. In this study, we used a recently established pathological model of TBEV infection based on human neuronal/glial cells differentiated from fetal neural progenitors and transcriptomic approaches to tackle this question. We confirmed the occurrence of apoptotic death in these cultures and further showed that genes involved in pyroptotic death were up-regulated, suggesting that this type of death also occurs in TBEV-infected human brain cells. On the contrary, no up-regulation of major autophagic genes was found. Furthermore, we demonstrated an up-regulation of a cluster of genes belonging to the extrinsic apoptotic pathway and revealed the cellular types expressing them. Our results suggest that neuronal death occurs by multiple mechanisms in TBEV-infected human neuronal/glial cells, thus providing a first insight into the molecular pathways that may be involved in neuronal death when the human brain is infected by TBEV.Mazigh FaresKamila GornaNoémie BerryMarielle Cochet-BernoinFrançois PiumiOdile BlanchetNadia HaddadJennifer RichardsonMuriel CoulpierMDPI AGarticlecentral nervous systemflavivirusneuronal deathpathological modelingtick-borne encephalitis virusTNF family membersMicrobiologyQR1-502ENViruses, Vol 13, Iss 2255, p 2255 (2021)
institution DOAJ
collection DOAJ
language EN
topic central nervous system
flavivirus
neuronal death
pathological modeling
tick-borne encephalitis virus
TNF family members
Microbiology
QR1-502
spellingShingle central nervous system
flavivirus
neuronal death
pathological modeling
tick-borne encephalitis virus
TNF family members
Microbiology
QR1-502
Mazigh Fares
Kamila Gorna
Noémie Berry
Marielle Cochet-Bernoin
François Piumi
Odile Blanchet
Nadia Haddad
Jennifer Richardson
Muriel Coulpier
Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal/Glial Cells
description Tick-borne encephalitis virus (TBEV), a member of the <i>Flaviviridae</i> family, <i>Flavivirus</i> genus, is responsible for neurological symptoms that may cause permanent disability or death. With an incidence on the rise, it is the major arbovirus affecting humans in Central/Northern Europe and North-Eastern Asia. Neuronal death is a critical feature of TBEV infection, yet little is known about the type of death and the molecular mechanisms involved. In this study, we used a recently established pathological model of TBEV infection based on human neuronal/glial cells differentiated from fetal neural progenitors and transcriptomic approaches to tackle this question. We confirmed the occurrence of apoptotic death in these cultures and further showed that genes involved in pyroptotic death were up-regulated, suggesting that this type of death also occurs in TBEV-infected human brain cells. On the contrary, no up-regulation of major autophagic genes was found. Furthermore, we demonstrated an up-regulation of a cluster of genes belonging to the extrinsic apoptotic pathway and revealed the cellular types expressing them. Our results suggest that neuronal death occurs by multiple mechanisms in TBEV-infected human neuronal/glial cells, thus providing a first insight into the molecular pathways that may be involved in neuronal death when the human brain is infected by TBEV.
format article
author Mazigh Fares
Kamila Gorna
Noémie Berry
Marielle Cochet-Bernoin
François Piumi
Odile Blanchet
Nadia Haddad
Jennifer Richardson
Muriel Coulpier
author_facet Mazigh Fares
Kamila Gorna
Noémie Berry
Marielle Cochet-Bernoin
François Piumi
Odile Blanchet
Nadia Haddad
Jennifer Richardson
Muriel Coulpier
author_sort Mazigh Fares
title Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal/Glial Cells
title_short Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal/Glial Cells
title_full Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal/Glial Cells
title_fullStr Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal/Glial Cells
title_full_unstemmed Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal/Glial Cells
title_sort transcriptomic studies suggest a coincident role for apoptosis and pyroptosis but not for autophagic neuronal death in tbev-infected human neuronal/glial cells
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/5de4f915746941d6940647ff896ac8da
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