Next Article in Journal
Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins
Next Article in Special Issue
Rabies in the African Civet: An Incidental Host for Lyssaviruses?
Previous Article in Journal
Genetic Strain Diversity of Multi-Host RNA Viruses that Infect a Wide Range of Pollinators and Associates is Shaped by Geographic Origins
Previous Article in Special Issue
Serological Survey of Lyssaviruses in Polish Bats in the Frame of Passive Rabies Surveillance Using an Enzyme-Linked Immunosorbent Assay
Open AccessArticle

Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures

1
Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australian Animal Health Laboratory (AAHL), East Geelong, VIC 3219, Australia
2
Monash Institute of Pharmaceutical Sciences, 399 Royal Parade, Parkville, VIC 3052, Australia
3
CSIRO Manufacturing, Research Way, Clayton, VIC 3168, Australia
4
Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3168, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Viruses 2020, 12(4), 359; https://doi.org/10.3390/v12040359
Received: 28 December 2019 / Revised: 2 March 2020 / Accepted: 20 March 2020 / Published: 25 March 2020
(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)
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. View Full-Text
Keywords: rabies; lyssavirus; stem cell-derived neurons; ex-vivo models; viral pathogenesis; trans-synaptic axonal trafficking; chemokine and cytokine response; neuronal apoptosis rabies; lyssavirus; stem cell-derived neurons; ex-vivo models; viral pathogenesis; trans-synaptic axonal trafficking; chemokine and cytokine response; neuronal apoptosis
Show Figures

Figure 1

MDPI and ACS Style

Sundaramoorthy, V.; Godde, N.; J. Farr, R.; Green, D.; M. Haynes, J.; Bingham, J.; O’Brien, C.M.; Dearnley, M. Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures. Viruses 2020, 12, 359.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop