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Home / Equine Research Bank / Stem Cells Dev / Cortical Neurons Derived from Equine Induced Pluripotent Ste...
Stem cells and development2018; 27(10); 704-715; doi: 10.1089/scd.2017.0106

Cortical Neurons Derived from Equine Induced Pluripotent Stem Cells Are Susceptible to Neurotropic Flavivirus Infection and Replication: An In Vitro Model for Equine Neuropathic Diseases.

Abstract: Horses are susceptible to a number of neurotropic viruses, including West Nile virus (WNV), which is a pathogen of global significance in both horses and humans. However, there are no in vitro models with which to study infectious neuropathic diseases in the horse. In an effort to redress this, we have generated neurons from equine induced pluripotent stem cells (equiPSCs) that express a range of cortical neuron-specific markers, in addition to the membrane-bound ligand ephrin B3, which plays an important role in axon guidance as well as functioning as the receptor through which henipaviruses, such as Hendra virus, enter mammalian neurons. EquiPSC-derived neurons spontaneously depolarize with waves of depolarization conducted unidirectionally to adjacent neurons. We sought to confirm that equiPSC-derived neurons are a possible in vitro model for viral neuropathic diseases in the horse by examining their susceptibility to infection with flaviviruses that are known to be neurotropic in horses, including WNV and Murray Valley encephalitis virus (MVEV), and to compare these to nonpathogenic flaviviruses such as Fitzroy River virus (FRV) and Bamaga virus (BgV). All three strains of WNV tested in this study grew to high titres in the equiPSC-derived neurons, inducing a strong cytopathic effect (cpe), as did MVEV. In contrast, FRV showed restricted replication, and no cpe, which is consistent with the observation that FRV infects, but does not cause disease, in horses. BgV, which is thought to infect only marsupials, did not replicate in the equiPSC-derived neurons. Hence, our equiPSC-derived neurons display virus-specific differences in terms of viral titre and cpe that are similar to observations made in vivo, thus supporting their use as an in vitro model for neurotropic viral infection in horses.
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Publication Date: 2018-04-16 PubMed ID: 29562867DOI: 10.1089/scd.2017.0106Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The researchers created neurons from horse induced pluripotent stem cells and demonstrated their potential as a model for studying horse neural diseases. They showed these cells are susceptible to neurotropic virus infections similar to horses, making them a valuable tool in studying such diseases in vitro.

Research Methodology

  • The primary objective of this research was to create an in vitro model for studying infectious neuropathic diseases in horses. Researchers used equine induced pluripotent stem cells (equiPSCs) for this purpose.
  • The equiPSCs were induced to differentiate into cortical neurons expressing a range of neuron-specific markers including the membrane-bound ligand ephrin B3. Ephrin B3 is crucial for axon guidance and also functions as the receptor for certain viruses.

Results and Findings

  • The equiPSC-derived neurons spontaneously depolarized, transmitting these depolarization waves to nearby cells.
  • To verify the suitability of these equiPSC-derived neurons as a model for viral neuropathy studies, they were infected with flaviviruses, known to infect horses’ nervous system, such as West Nile virus (WNV) and Murray Valley encephalitis virus (MVEV).
  • The researchers also experimented with non-pathogenic flaviviruses like Fitzroy River virus (FRV) and Bamaga virus (BgV) for comparison.
  • All three strains of WNV used in the study reached high titres in the equiPSC-derived neurons and caused strong cytopathic effects (CPE). MVEV also demonstrated similar results.
  • The FRV showed limited replication and did not produce a noticeable cytopathic effect, in line with previous observations that FRV can infect horses without causing any disease.
  • On the contrary, BgV, typically found in marsupials, showed no signs of replication in equiPSC-derived neurons.

Conclusion

  • The equiPSC-derived neurons exhibited virus-specific differences in terms of viral titre and cytopathic effect, mirroring in vivo observations.
  • This research affirms the potential of equiPSC-derived neurons as an in vitro model for the study of neurotropic viral infections in horses.

Cite This Article

APA
Fortuna PRJ, Bielefeldt-Ohmann H, Ovchinnikov DA, Wolvetang EJ, Whitworth DJ. (2018). Cortical Neurons Derived from Equine Induced Pluripotent Stem Cells Are Susceptible to Neurotropic Flavivirus Infection and Replication: An In Vitro Model for Equine Neuropathic Diseases. Stem Cells Dev, 27(10), 704-715. https://doi.org/10.1089/scd.2017.0106

Publication

Stem cells and development
ISSN: 1557-8534
NlmUniqueID: 101197107
Country: United States
Language: English
Volume: 27
Issue: 10
Pages: 704-715

Researcher Affiliations

Fortuna, Patrick R J
  • 1 Australian Institute for Bioengineering and Nanotechnology, University of Queensland , St Lucia, Australia .
Bielefeldt-Ohmann, Helle
  • 2 School of Veterinary Science, University of Queensland , Gatton, Australia .
  • 3 Australian Infectious Diseases Research Centre, University of Queensland , St Lucia, Australia .
Ovchinnikov, Dmitry A
  • 1 Australian Institute for Bioengineering and Nanotechnology, University of Queensland , St Lucia, Australia .
Wolvetang, Ernst J
  • 1 Australian Institute for Bioengineering and Nanotechnology, University of Queensland , St Lucia, Australia .
Whitworth, Deanne J
  • 1 Australian Institute for Bioengineering and Nanotechnology, University of Queensland , St Lucia, Australia .
  • 2 School of Veterinary Science, University of Queensland , Gatton, Australia .

MeSH Terms

  • Animals
  • Flavivirus / pathogenicity
  • Flavivirus Infections / virology
  • Horse Diseases / virology
  • Horses
  • Induced Pluripotent Stem Cells / virology
  • Neurons / virology
  • Virus Replication / physiology
  • West Nile Fever / virology
  • West Nile virus / pathogenicity

Citations

This article has been cited 8 times.
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