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Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures

Sundaramoorthy, Vinod, Godde, Nathan, Farr, Ryan J., Green, Diane, Haynes, John M., Bingham, John, O'Brien, Carmel M. and Dearnley, Megan 2020, Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures, Viruses, vol. 12, no. 4, pp. 1-24, doi: 10.3390/v12040359.

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Title Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures
Author(s) Sundaramoorthy, VinodORCID iD for Sundaramoorthy, Vinod orcid.org/0000-0001-6309-8031
Godde, Nathan
Farr, Ryan J.
Green, Diane
Haynes, John M.
Bingham, John
O'Brien, Carmel M.
Dearnley, Megan
Journal name Viruses
Volume number 12
Issue number 4
Start page 1
End page 24
Total pages 24
Publisher MDPI
Place of publication Basel, Switzerland
Publication date 2020-04-01
ISSN 1999-4915
1999-4915
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Virology
rabies
lyssavirus
stem cell-derived neurons
ex-vivo models
viral pathogenesis
trans-synaptic axonal trafficking
chemokine and cytokine response
neuronal apoptosis
BLOOD-BRAIN-BARRIER
RABIES VIRUS PHOSPHOPROTEIN
CENTRAL-NERVOUS-SYSTEM
NEURONAL CELLS
DIFFERENTIATION
EXPRESSION
PROTEIN
ACTIVATION
APOPTOSIS
CCL5
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.
Language eng
DOI 10.3390/v12040359
Indigenous content off
Field of Research 0605 Microbiology
HERDC Research category C1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30136876

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.