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.

Viruses
|November 27, 2021
PubMed

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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