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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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) |
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central nervous system flavivirus neuronal death pathological modeling tick-borne encephalitis virus TNF family members Microbiology QR1-502 |
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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 |
work_keys_str_mv |
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1718410158158118912 |