Transcriptomic studies suggest a coincident role for apoptosis and pyroptosis but not for autophagic neuronal death in TBEV-infected human neuronal/glial cells

Fares, M. , Gorna, K., Berry, N., Cochet-Bernoin, M., Piumi, F., Blanchet, O., Haddad, N., Richardson, J. and Coulpier, M. (2021) Transcriptomic studies suggest a coincident role for apoptosis and pyroptosis but not for autophagic neuronal death in TBEV-infected human neuronal/glial cells. Viruses, 13(11), 2255. (doi: 10.3390/v13112255) (PMID:34835061) (PMCID:PMC8620470)

Abstract

Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, Flavivirus 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.

• Item Type: Articles
• Additional Information: This research was funded by the French National Research Institute for Agriculture, Food and Environment (INRAE) and the DIM MalInf (Ile de France). M.F. was financially supported by a PhD fellowship from INRAE and the Paris Institute of technology for life, food, and environmental sciences (AgroParisTech). N.B. is financially supported by the DIM One Health (Ile de France).
• Keywords: Central nervous system, flavivirus, neuronal death, pathological modeling, tick-borne encephalitis virus, TNF family members, regulated cell death.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Fares, Dr Mazigh

Creator Roles

Fares, M.: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Writing – review and editing

• Authors: Fares, M., Gorna, K., Berry, N., Cochet-Bernoin, M., Piumi, F., Blanchet, O., Haddad, N., Richardson, J., and Coulpier, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Viruses
• Publisher: MDPI
• ISSN: 1999-4915
• ISSN (Online): 1999-4915
• Published Online: 10 November 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Viruses 13(11): 2255
• Publisher Policy: Reproduced under a Creative Commons License