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Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death
Mazigh Fares1,2, Kamila Gorna1, Noémie Berry1
1UMR1161 Virologie, Anses, INRAE, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, F-94700 Maisons-Alfort, France.
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.
Insights
Tick-borne encephalitis virus (TBEV) causes rising neurological disease. This study reveals TBEV infection induces multiple cell death pathways, including apoptosis and pyroptosis, in human brain cells.
Area of Science:
- Neuroscience
- Virology
- Cell Biology
Background:
- Tick-borne encephalitis virus (TBEV) is a significant arbovirus causing severe neurological illness in Europe and Asia.
- Neuronal death is a key pathological feature of TBEV infection, but the underlying molecular mechanisms remain largely unknown.
Purpose of the Study:
- To investigate the specific types and molecular mechanisms of neuronal death induced by TBEV infection in human brain cells.
- To elucidate the cellular pathways involved in TBEV-induced neuropathology.
Main Methods:
- Utilized a human neuronal/glial cell model derived from fetal neural progenitors.
- Employed transcriptomic analysis to identify gene expression changes.
- Confirmed apoptotic cell death and assessed genes related to pyroptosis and autophagy.
Main Results:
- Confirmed apoptotic cell death in TBEV-infected human neuronal/glial cells.
- Observed up-regulation of genes associated with pyroptotic death, suggesting its involvement.
- Found no significant up-regulation of major autophagic genes.
- Identified up-regulation of genes in the extrinsic apoptotic pathway and the specific cell types expressing them.
Conclusions:
- Neuronal death in TBEV infection involves multiple mechanisms, including apoptosis and pyroptosis.
- Provides initial insights into the molecular pathways driving TBEV neuropathogenesis.
- Highlights the complexity of TBEV's impact on the human brain.
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