Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures

Rabies is a zoonotic neurological infection caused by lyssavirus that continues to result in devastating loss of human life. Many aspects of rabies pathogenesis in human neurons are not well understood. Lack of appropriate ex-vivo models for studying rabies infection in human neurons has contributed...

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Bibliographic Details
Published in:Viruses 2020-03, Vol.12 (4), p.359
Main Authors: Sundaramoorthy, Vinod, Godde, Nathan, Farr, Ryan J, Green, Diane, Haynes, John M, Bingham, John, O'Brien, Carmel M, Dearnley, Megan
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Axons - metabolism
Axons - virology
Biomarkers
Calcium - metabolism
Cell Survival
Cells, Cultured
chemokine and cytokine response
Chemokines - metabolism
Cytokines - metabolism
Disease transmission
ex-vivo models
Host-Pathogen Interactions
Human cell culture
Humans
Immunohistochemistry
lyssavirus
Lyssavirus - physiology
Mice
Molecular Imaging
neuronal apoptosis
Neurons
Neurons - virology
Rabies
Rabies virus - physiology
Rhabdoviridae Infections - virology
Stem cell research
stem cell-derived neurons
Stem Cells - cytology
Stem Cells - metabolism
trans-synaptic axonal trafficking
viral pathogenesis
Zoonoses
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Summary:Rabies is a zoonotic neurological infection caused by lyssavirus that continues to result in devastating loss of human life. Many aspects of rabies pathogenesis in human neurons are not well understood. Lack of appropriate ex-vivo models for studying rabies infection in human neurons has contributed to this knowledge gap. In this study, we utilize advances in stem cell technology to characterize rabies infection in human stem cell-derived neurons. We show key cellular features of rabies infection in our human neural cultures, including upregulation of inflammatory chemokines, lack of neuronal apoptosis, and axonal transmission of viruses in neuronal networks. In addition, we highlight specific differences in cellular pathogenesis between laboratory-adapted and field strain lyssavirus. This study therefore defines the first stem cell-derived ex-vivo model system to study rabies pathogenesis in human neurons. This new model system demonstrates the potential for enabling an increased understanding of molecular mechanisms in human rabies, which could lead to improved control methods.
ISSN:1999-4915
1999-4915
DOI:10.3390/v12040359