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Table of contents
Chapter I: Introduction
Tick-borne encephalitis virus
Genomic and structural organization
Replication cycle
1.2. Transmission and epidemiology of tick-borne encephalitis virus
1.2.1. Risk areas and endemic zone
1.2.2. Amplifying and spreading hosts
1.2.3. Biology of the vector
1.3. Tick-borne encephalitis
1.3.1. Clinical presentation in humans
1.3.2. Vaccination against TBEV in humans
1.3.3. Viral pathogenesis
1.4. Cell response to TBEV infection
1.4.1. Intrinsic immune response
1.4.2. Cell death
Objectives
Chapter II: Results
2.1. TBEV infects human brain cells differentiated from fetal neural progenitors
2.2. TBEV infects human neurons, astrocytes, and oligodendrocytes
2.3. TBEV induces massive neuronal loss whereas it moderately affects glial cells viability
2.4. TBEV-induced cell death: apoptosis or autophagy?
2.5. Human neural cells develop a strong antiviral response to TBEV infection
2.6. TBEV induces an antiviral response in human neurons and human astrocytes
2.6.1. Experimental design for enrichment of neurons and astrocytes
2.6.2. Antiviral response to TBEV infection is weaker in human neurons than in human astrocytes
2.7. Complex interplay between neurons and astrocytes modulates TBEV infection in each cell type
2.7.1. Astrocytes modulate TBEV infection in neurons
2.7.2. Neurons modulate astrocytes fate in TBEV-infected cells
2.8. Preliminary data: siRNA transfections to downregulate PRRs
Chapter III: Discussion
Material and methods
Human neural progenitor cells culture
Neural stem cells differentiation
Virus and infection
Cell transfection
Intracellular RNA extraction
Viral RNA extraction
PCR array analysis
Reverse transcription and quantitative polymerase chain reaction analysis
Immunofluorescence and TUNEL analyses
Magnetic-activated cell sorting
Statistical analyses
References
Supplementary information
