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Home / Equine Research Bank / Viruses / Bovine Papillomavirus Type 1 or 2 Virion-Infected Primary Fi...
Viruses2022; 14(12); 2658; doi: 10.3390/v14122658

Bovine Papillomavirus Type 1 or 2 Virion-Infected Primary Fibroblasts Constitute a Near-Natural Equine Sarcoid Model.

Abstract: Equine sarcoids are common, locally aggressive skin tumors induced by bovine papillomavirus types 1, 2, and possibly 13 (BPV1, BPV2, BPV13). Current in vitro models do not mimic de novo infection. We established primary fibroblasts from horse skin and succeeded in infecting these cells with native BPV1 and BPV2 virions. Subsequent cell characterization was carried out by cell culture, immunological, and molecular biological techniques. Infection of fibroblasts with serial 10-fold virion dilutions (2 × 10-20 virions) uniformly led to DNA loads settling at around 150 copies/cell after four passages. Infected cells displayed typical features of equine sarcoid cells, including hyperproliferation, and loss of contact inhibition. Neither multiple passaging nor storage negatively affected cell hyperproliferation, viral DNA replication, and gene transcription, suggestive for infection-mediated cell immortalization. Intriguingly, extracellular vesicles released by BPV1-infected fibroblasts contained viral DNA that was most abundant in the fractions enriched for apoptotic bodies and exosomes. This viral DNA is likely taken up by non-infected fibroblasts. We conclude that equine primary fibroblasts stably infected with BPV1 and BPV2 virions constitute a valuable near-natural model for the study of yet unexplored mechanisms underlying the pathobiology of BPV1/2-induced sarcoids.
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Publication Date: 2022-11-28 PubMed ID: 36560661PubMed Central: PMC9781842DOI: 10.3390/v14122658Google Scholar: Lookup
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  • 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.

This research article explores how primary fibroblasts, cells derived from horse skin, infected with bovine papillomavirus types 1, 2, and potentially 13, can form a representative model for studying equine sarcoids, which are common and aggressive skin tumors in horses.

Understanding the Model System

  • The researchers used primary fibroblasts, which are a type of cell found in horse skin. They infected these cells with bovine papillomavirus (BPV) types 1, 2, and possibly 13. These specific viruses are known to induce equine sarcoids, – a common and locally aggressive skin tumor in horses.
  • The existing in-vitro models – experiments performed in a controlled environment outside a living organism – failed to replicate de novo infection, the natural process where viruses infect cells leading to the disease. This led the researchers to develop a new model that could accurately imitate real-life infections.

Infection Process and Results

  • The infection of fibroblasts was carried out using varying amounts of BPV1 and BPV2 virions, with DNA loads settling at around 150 copies per cell after four iterations.
  • The success of the infection process was confirmed through cell culture, immunological, and molecular biological techniques.
  • As a result, the infected cells displayed features typical of equine sarcoid cells, including hyperproliferation and loss of contact inhibition, which is the regulation preventing cells from dividing and infecting adjacent cells.
  • The researchers observed that the cell’s hyperproliferation, viral DNA replication, and gene transcription were not adversely affected by multiple rounds of cell division or storage, suggesting the possible immortalization of cells mediated by the infection.

Extracellular Vesicles and Viral DNA

  • A significant observation made was the presence of viral DNA in the extracellular vesicles, specifically in apoptotic bodies and exosomes, released by the BPV1-infected fibroblasts. Extracellular vesicles are tiny, membrane-bound particles that cells secrete, carrying various molecular constituents of their parent cell. Apoptotic bodies and exosomes are types of such vesicles.
  • The presence of viral DNA in these vesicles indicates that they could be taken up by non-infected fibroblasts, potentially leading to the spread of the virus.

Conclusion

  • Based on their results, the researchers concluded that equine primary fibroblasts infected with BPV1 and BPV2 serve as a valuable and representative model for further understanding the pathobiology of BPV-induced sarcoids.
  • This new model could become a crucial tool for studying unidentified mechanisms behind BPV-induced sarcoids, aiding in the development of novel therapeutic strategies for treating this common skin disease in horses.

Cite This Article

APA
Hainisch EK, Jindra C, Reicher P, Miglinci L, Brodesser DM, Brandt S. (2022). Bovine Papillomavirus Type 1 or 2 Virion-Infected Primary Fibroblasts Constitute a Near-Natural Equine Sarcoid Model. Viruses, 14(12), 2658. https://doi.org/10.3390/v14122658

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 14
Issue: 12
PII: 2658

Researcher Affiliations

Hainisch, Edmund K
  • Research Group Oncology, Equine Surgery, Equine Clinic, University of Veterinary Medicine, 1210 Vienna, Austria.
Jindra, Christoph
  • Research Group Oncology, Equine Surgery, Equine Clinic, University of Veterinary Medicine, 1210 Vienna, Austria.
  • Division Molecular Oncology and Haematology, Karl Landsteiner University of Health Sciences, 3500 Krems an der Donau, Austria.
Reicher, Paul
  • Research Group Oncology, Equine Surgery, Equine Clinic, University of Veterinary Medicine, 1210 Vienna, Austria.
Miglinci, Lea
  • Research Group Oncology, Equine Surgery, Equine Clinic, University of Veterinary Medicine, 1210 Vienna, Austria.
Brodesser, Daniela M
  • Research Group Oncology, Equine Surgery, Equine Clinic, University of Veterinary Medicine, 1210 Vienna, Austria.
Brandt, Sabine
  • Research Group Oncology, Equine Surgery, Equine Clinic, University of Veterinary Medicine, 1210 Vienna, Austria.

MeSH Terms

  • Horses
  • Animals
  • Bovine papillomavirus 1 / genetics
  • DNA, Viral / genetics
  • DNA Replication
  • Papillomavirus Infections
  • Virus Replication
  • Virion
  • Fibroblasts / pathology
  • Horse Diseases

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Citations

This article has been cited 4 times.
  1. Jindra C, Hainisch EK, Brandt S. Immunotherapy of Equine Sarcoids-From Early Approaches to Innovative Vaccines. Vaccines (Basel) 2023 Mar 30;11(4).
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  4. De Falco F, Cutarelli A, Pellicanò R, Brandt S, Roperto S. Molecular Detection and Quantification of Ovine Papillomavirus DNA in Equine Sarcoid. Transbound Emerg Dis 2024;2024:6453158.
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