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Folia microbiologica2017; 63(1); 1-11; doi: 10.1007/s12223-017-0528-5

Influence of long-term equine herpesvirus type 1 (EHV-1) infection on primary murine neurons-the possible effects of the multiple passages of EHV-1 on its neurovirulence.

Abstract: Equine herpesvirus 1 (EHV-1), like other members of the Alphaherpesvirinae subfamily, is a neurotropic virus causing latent infections in the nervous system of the natural host. In the present study, we have investigated EHV-1 replication (wild-type Jan-E strain and Rac-H laboratory strain) during long-term infection and during the passages of the virus in cultured neurons. The studies were performed on primary murine neurons, which are an excellent in vitro model for studying neurotropism and neurovirulence of EHV-1. Using real-time cell growth analysis, we have demonstrated for the first time that primary murine neurons are able to survive long-term EHV-1 infection. Positive results of real-time PCR test indicated a high level of virus DNA in cultured neurons, and during long-term infection, these neurons were still able to transmit the virus to the other cells. We also compared the neurovirulence of Rac-H and Jan-E EHV-1 strains after multiple passages of these strains in neuron cell culture. The results showed that multiple passages of EHV-1 in neurons lead to the inhibition of viral replication as early as in the third passage. Interestingly, the inhibition of the EHV-1 replication occurred exclusively in neurons, because the equine dermal (ED) cells co-cultivated with neuroculture medium from the third passage showed the presence of large amount of viral DNA. In conclusion, our results showed that certain balance between EHV-1 and neurons has been established during in vitro infection allowing neurons to survive long-term infection.
Publication Date: 2017-04-13 PubMed ID: 28409422PubMed Central: PMC5733002DOI: 10.1007/s12223-017-0528-5Google Scholar: Lookup
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  • Journal Article

Summary

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The research focuses on exploring how long-term infection of equine herpesvirus type 1 (EHV-1) behaves in primary murine neurons to understand the virus’s neurovirulence and neurotropism. A notable finding is that despite high levels of virus DNA present, the neurons could survive long-term infection and still transfer the virus to other cells.

Investigation of EHV-1 Replication

  • The bulk of the investigation revolves around the behavior of EHV-1 during long-term infection and subsequent passages in cultured neurons. Two strains of EHV-1 were put under examination: the wild-type Jan-E and the laboratory Rac-H.
  • The researchers used primary murine neurons to replicate the impact on a live host’s nervous system. This in vitro model has been known to provide valuable data on the virus’s neurovirulence and neurotropism.

Survival of Neurons during Long-Term EHV-1 Infection

  • A significant discovery of the study is that despite long-term EHV-1 infection, primary murine neurons could survive. The researchers achieved this conclusion via real-time cell growth analysis.
  • Surprisingly, high levels of viral DNA were found in these long-term infected neurons. Despite this, the neurons were still capable of passing on the virus to other cells.
  • This information is crucial as it provides insights about EHV-1 being a latent infection, which means, it stays dormant in the host’s body but can still spread and reactivate.

Influence of Multiple Passages of EHV-1 on its Neurovirulence

  • The study makes a comparison of the neurovirulence of the Jan-E and Rac-H EHV-1 strains after these had been cultured multiple times in neuron cells.
  • An interesting outcome was that after being cultured repeatedly – from the third passage onwards – the replication of the virus was inhibited. However, this occurred exclusively in the neurons.
  • In contrast, equine dermal (horse skin) cells co-cultured with neuroculture medium from the third passage showed a large presence of viral DNA. This suggests that the virus was still replicating in these cells and was not limited, unlike the neurons.

Conclusion

  • The study concludes with a theory that primary murine neurons develop a certain equilibrium with EHV-1 during long-term in vitro infection, which allows the neurons to survive and also suggests the capacity of the virus to adapt to its host environment.

Cite This Article

APA
Cymerys J, Słońska A, Tucholska A, Golke A, Chmielewska A, Bańbura MW. (2017). Influence of long-term equine herpesvirus type 1 (EHV-1) infection on primary murine neurons-the possible effects of the multiple passages of EHV-1 on its neurovirulence. Folia Microbiol (Praha), 63(1), 1-11. https://doi.org/10.1007/s12223-017-0528-5

Publication

ISSN: 1874-9356
NlmUniqueID: 0376757
Country: United States
Language: English
Volume: 63
Issue: 1
Pages: 1-11

Researcher Affiliations

Cymerys, Joanna
  • Division of Microbiology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Ciszewskiego 8, 02-786, Warsaw, Poland. jcymerys@op.pl.
Słońska, A
  • Division of Microbiology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Ciszewskiego 8, 02-786, Warsaw, Poland.
Tucholska, A
  • Division of Microbiology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Ciszewskiego 8, 02-786, Warsaw, Poland.
Golke, A
  • Division of Microbiology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Ciszewskiego 8, 02-786, Warsaw, Poland.
Chmielewska, A
  • Division of Microbiology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Ciszewskiego 8, 02-786, Warsaw, Poland.
Bańbura, M W
  • Division of Microbiology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Ciszewskiego 8, 02-786, Warsaw, Poland.

MeSH Terms

  • Animals
  • Cells, Cultured
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / virology
  • Herpesvirus 1, Equid / genetics
  • Herpesvirus 1, Equid / growth & development
  • Herpesvirus 1, Equid / pathogenicity
  • Herpesvirus 1, Equid / physiology
  • Horse Diseases / virology
  • Horses
  • Host Specificity
  • Mice
  • Mice, Inbred BALB C
  • Neurons / virology
  • Serial Passage
  • Virulence
  • Virus Replication

Grant Funding

  • NN308 028 739 / Polish Ministry of Science and Higher Education

Conflict of Interest Statement

All animals were handled and cared for according to Polish and European Animal Care and Use guidelines and regulations. All procedures involving live animals were approved by a Local Ethics Committee and confirmed to applicable international standards agreement no. 24/2012. COMPETING INTERESTS: The authors declare that they have no competing interests.

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Citations

This article has been cited 2 times.
  1. Song H, Xun S, He H, Duan C, Li Q. Compound Porcine Cerebroside and Ganglioside Injection (CPCGI) Attenuates Sevoflurane-Induced Nerve Cell Injury by Regulating the Phosphorylation of p38 MAP Kinase (p38MAPK)/Nuclear Factor kappa B (NF-κB) Pathway.. Med Sci Monit 2020 Mar 1;26:e919600.
    doi: 10.12659/MSM.919600pubmed: 32114591google scholar: lookup
  2. Chodkowski M, Serafińska I, Brzezicka J, Golke A, Słońska A, Krzyżowska M, Orłowski P, Bąska P, Bańbura MW, Cymerys J. Human herpesvirus type 1 and type 2 disrupt mitochondrial dynamics in human keratinocytes.. Arch Virol 2018 Oct;163(10):2663-2673.
    doi: 10.1007/s00705-018-3890-ypubmed: 29872950google scholar: lookup