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Veterinary microbiology2015; 178(1-2); 132-137; doi: 10.1016/j.vetmic.2015.04.018

In vivo assessment of equine arteritis virus vaccine improvement by disabling the deubiquitinase activity of papain-like protease 2.

Abstract: Arteriviruses are a family of positive-stranded RNA viruses that includes the prototypic equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV). Although several vaccines against these viruses are commercially available there is room for improvement, especially in the case of PRRSV. The ability of arteriviruses to counteract the immune response is thought to decrease the efficacy of the current modified live virus vaccines. We have recently shown that the deubiquitinase (DUB) activity of EAV papain-like protease 2 (PLP2) is important for the inhibition of innate immune activation during infection. A vaccine virus lacking PLP2 DUB activity may therefore be more immunogenic and provide improved protection against subsequent challenge than its DUB-competent counterpart. To test this hypothesis, twenty Shetland mares were randomly assigned to one of three groups. Two groups were vaccinated, either with DUB-positive (n=9) or DUB-negative (n=9) recombinant EAV. The third group (n=2) was not vaccinated. All horses were subsequently challenged with the virulent KY84 strain of EAV. Both vaccine viruses proved to be replication competent in vivo. In addition, the DUB-negative virus provided a similar degree of protection against clinical disease as its DUB-positive parental counterpart. Owing to the already high level of protection provided by the parental virus, a possible improvement due to inactivation of PLP2 DUB activity could not be detected under these experimental conditions. Taken together, the data obtained in this study warrant further in vivo investigations into the potential of using DUB-mutant viruses for the improvement of arterivirus vaccines.
Copyright © 2015 Elsevier B.V. All rights reserved.
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Publication Date: 2015-04-30 PubMed ID: 25975520PubMed Central: PMC7117436DOI: 10.1016/j.vetmic.2015.04.018Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • 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 research article investigates the possibility of improving equine arteritis virus vaccines by disabling the papain-like protease 2 (PLP2) deubiquitinase (DUB) activity. The study used Shetland mares and tested vaccine viruses, both DUB-positive and DUB-negative, to measure their effectiveness in protection against a virulent strain of equine arteritis virus.

Overview of the Study

  • The study focused on arteriviruses, a family of positive-stranded RNA viruses that includes equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV).
  • Although vaccines are available against these viruses, the capacity of arteriviruses to hinder immune responses is believed to reduce the effectiveness of the existing vaccines.
  • The researchers recently discovered that the deubiquitinase (DUB) activity of EAV’s papain-like protease 2 (PLP2) is crucial for inhibiting innate immune activation during an infection.
  • Hence, the study hypothesized that a vaccine virus without PLP2 DUB activity might trigger better immunogenic response and offer superior protection compared to the DUB-competent one.

Implementation and Results

  • To validate the hypothesis, the researchers divided twenty Shetland mares into three groups. Two groups were vaccinated with either DUB-positive (n=9) or DUB-negative (n=9) recombinant EAV. The third group (n=2) was left unvaccinated.
  • All mares were then exposed to the virulent KY84 strain of EAV.
  • The results confirmed that both vaccine viruses – DUB-positive and DUB-negative – could competently replicate in vivo.
  • Also, the DUB-negative virus yielded a similar protection level against clinical disease as its DUB-positive counterpart.
  • However, due to the high protection level already provided by the DUB-positive virus, an improvement resulting from the inactivation of PLP2 DUB activity couldn’t be identified in this experimental framework.

Conclusion and Future Scope

  • Despite the inconclusive results, the research encourages further in vivo investigations into the potential of employing DUB-mutant viruses to enhance the potency of arterivirus vaccines.

The experiment provides a foundation for further exploration into the intricate relationship between virus and host immune system, potentially paving the way for more effective arterivirus vaccines.

Cite This Article

APA
van Kasteren PB, Knaap RC, van den Elzen P, Snijder EJ, Balasuriya UB, van den Born E, Kikkert M. (2015). In vivo assessment of equine arteritis virus vaccine improvement by disabling the deubiquitinase activity of papain-like protease 2. Vet Microbiol, 178(1-2), 132-137. https://doi.org/10.1016/j.vetmic.2015.04.018

Publication

Veterinary microbiology
ISSN: 1873-2542
NlmUniqueID: 7705469
Country: Netherlands
Language: English
Volume: 178
Issue: 1-2
Pages: 132-137

Researcher Affiliations

van Kasteren, Puck B
  • Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Knaap, Robert C M
  • Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
van den Elzen, Paul
  • MSD Animal Health, Wim de Körverstraat 35, 5831 AN Boxmeer, The Netherlands.
Snijder, Eric J
  • Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Balasuriya, Udeni B R
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, 1400 Nicholasville Road, 40546-0099 Lexington, KY, USA.
van den Born, Erwin
  • MSD Animal Health, Wim de Körverstraat 35, 5831 AN Boxmeer, The Netherlands.
Kikkert, Marjolein
  • Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Electronic address: m.kikkert@lumc.nl.

MeSH Terms

  • Animals
  • Arterivirus Infections / prevention & control
  • Arterivirus Infections / veterinary
  • Coronavirus Papain-Like Proteases
  • Equartevirus / enzymology
  • Equartevirus / immunology
  • Female
  • Horse Diseases / prevention & control
  • Horse Diseases / virology
  • Horses
  • Papain / genetics
  • Treatment Outcome
  • Ubiquitin-Specific Proteases / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, Attenuated / therapeutic use
  • Viral Vaccines / immunology
  • Viral Vaccines / therapeutic use

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Citations

This article has been cited 8 times.
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