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Virus research2009; 147(2); 176-181; doi: 10.1016/j.virusres.2009.10.017

The effect of siRNA treatment on experimental equine herpesvirus type 1 (EHV-1) infection in horses.

Abstract: Available vaccines fail to induce lasting and protective immunity to equine herpesvirus 1 (EHV-1) associated diseases. RNA interference is a novel approach showing promise for therapeutic use in outbreak situations. This study examined the effect of small interfering RNA (siRNA) on clinical signs as well as the presence of live virus and viral DNA in nasal secretions and peripheral blood mononuclear cells (PBMCs) in horses experimentally infected with EHV-1. siRNA targeting two EHV-1 genes (glycoprotein B and the origin binding protein) was administered 12h before and 12h after intranasal infection with EHV-1. Control horses received siRNA targeting firefly luciferase. A significantly smaller proportion (0/10) of horses receiving siRNA targeting viral genes required euthanasia due to intractable neurologic disease as compared to horses in the control group (3/4; p=0.01). There was no significant difference in the presence of live virus or viral DNA in the nasal secretions or PBMCs between the two groups. Future studies are necessary to define the relative contributions of host and virus factors in the development of the neurological form of the infection and to determine an optimal dosing regimen for metaphylactic or therapeutic use of siRNA for treating EHV-1 infection.
Publication Date: 2009-11-05 PubMed ID: 19896512PubMed Central: PMC7114471DOI: 10.1016/j.virusres.2009.10.017Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • 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 study explores the effects of small interfering RNA (siRNA) on horses infected with equine herpesvirus type 1 (EHV-1). The results indicate that siRNA, specifically targeting two EHV-1 genes, could potentially decrease the severity of symptoms in infected horses.

Research Context

  • This research is conducted in the backdrop of the failure of existing vaccines to provide long-lasting and protective immunity against EHV-1 related diseases in horses.
  • Given the current limitations, the research explores RNA interference as a potential therapeutic approach, as it has previously shown promise in the control of disease outbreaks.

Research Methodology

  • The research involved the experimental infection of horses with EHV-1 to study the impact of siRNA treatment.
  • The siRNA used specifically targeted two EHV-1 genes, glycoprotein B and the origin-binding protein, and was administered to the test horses 12 hours before and 12 hours after the intranasal infection.
  • Control horses were given siRNA that targeted firefly luciferase, which is unrelated to EHV-1, to provide a baseline for comparison.

Research Findings

  • The study found that a notably smaller proportion of the horses receiving siRNA targeting the EHV-1 viral genes needed euthanasia due to severe neurological disease compared to the control group horses.
  • Although the impact on the severity of symptoms was evident, the research noted no significant difference in the presence of the live EHV-1 virus or its DNA in the nasal secretions or peripheral blood mononuclear cells (PBMCs) between the treated and control group.

Implications and Future Direction

  • These findings suggest that siRNA treatment can be potentially used for treating EHV-1 infection in horses in the future.
  • However, there is a need for further studies to elucidate the interaction of host and virus factors in the development of the neurological form of EHV-1 infection, as well as the determination of an optimal dosage regimen for prophylactic or therapeutic use of siRNA.

Cite This Article

APA
Brosnahan MM, Damiani A, van de Walle G, Erb H, Perkins GA, Osterrieder N. (2009). The effect of siRNA treatment on experimental equine herpesvirus type 1 (EHV-1) infection in horses. Virus Res, 147(2), 176-181. https://doi.org/10.1016/j.virusres.2009.10.017

Publication

ISSN: 1872-7492
NlmUniqueID: 8410979
Country: Netherlands
Language: English
Volume: 147
Issue: 2
Pages: 176-181

Researcher Affiliations

Brosnahan, Margaret M
  • Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
Damiani, Armando
    van de Walle, Gerlinde
      Erb, Hollis
        Perkins, Gillian A
          Osterrieder, Nikolaus

            MeSH Terms

            • Animals
            • Antiviral Agents / administration & dosage
            • Antiviral Agents / therapeutic use
            • Blood / virology
            • Bodily Secretions / virology
            • DNA, Viral / genetics
            • DNA, Viral / isolation & purification
            • Female
            • Herpesviridae Infections / drug therapy
            • Herpesviridae Infections / pathology
            • Herpesviridae Infections / veterinary
            • Herpesviridae Infections / virology
            • Herpesvirus 1, Equid / genetics
            • Horse Diseases / drug therapy
            • Horse Diseases / pathology
            • Horse Diseases / virology
            • Horses
            • Leukocytes, Mononuclear / virology
            • Male
            • Nose / virology
            • Pregnancy
            • RNA, Small Interfering / administration & dosage
            • RNA, Small Interfering / genetics
            • RNA, Small Interfering / therapeutic use
            • Survival Analysis
            • Time Factors

            References

            This article includes 29 references
            1. Allen GP. Risk factors for development of neurologic disease after experimental exposure to equine herpesvirus-1 in horses.. Am J Vet Res 2008 Dec;69(12):1595-600.
              pubmed: 19046006doi: 10.2460/ajvr.69.12.1595google scholar: lookup
            2. Allen GP, Bolin DC, Bryant U, Carter CN, Giles RC, Harrison LR, Hong CB, Jackson CB, Poonacha K, Wharton R, Williams NM. Prevalence of latent, neuropathogenic equine herpesvirus-1 in the Thoroughbred broodmare population of central Kentucky.. Equine Vet J 2008 Mar;40(2):105-10.
              pubmed: 18089469doi: 10.2746/042516408x253127google scholar: lookup
            3. Allen GP, Breathnach CC. Quantification by real-time PCR of the magnitude and duration of leucocyte-associated viraemia in horses infected with neuropathogenic vs. non-neuropathogenic strains of EHV-1.. Equine Vet J 2006 May;38(3):252-7.
              pubmed: 16706281doi: 10.2746/042516406776866453google scholar: lookup
            4. Bartlett DW, Davis ME. Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging.. Nucleic Acids Res 2006;34(1):322-33.
              pmc: PMC1331994pubmed: 16410612doi: 10.1093/nar/gkj439google scholar: lookup
            5. Bentz BG, Maxwell LK, Erkert RS, Royer CM, Davis MS, MacAllister CG, Clarke CR. Pharmacokinetics of acyclovir after single intravenous and oral administration to adult horses.. J Vet Intern Med 2006 May-Jun;20(3):589-94.
            6. Foote CE, Love DN, Gilkerson JR, Whalley JM. Detection of EHV-1 and EHV-4 DNA in unweaned Thoroughbred foals from vaccinated mares on a large stud farm.. Equine Vet J 2004 May;36(4):341-5.
              pubmed: 15163042doi: 10.2746/0425164044890634google scholar: lookup
            7. Fulton A, Peters ST, Perkins GA, Jarosinski KW, Damiani A, Brosnahan M, Buckles EL, Osterrieder N, Van de Walle GR. Effective treatment of respiratory alphaherpesvirus infection using RNA interference.. PLoS One 2009;4(1):e4118.
            8. Furr M, Reed S. Neurologic Examination, Equine Neurology. pp. 65–76.
            9. Garré B, Gryspeerdt A, Croubels S, De Backer P, Nauwynck H. Evaluation of orally administered valacyclovir in experimentally EHV1-infected ponies.. Vet Microbiol 2009 Mar 30;135(3-4):214-21.
              pubmed: 18986780doi: 10.1016/j.vetmic.2008.09.062google scholar: lookup
            10. Garré B, van der Meulen K, Nugent J, Neyts J, Croubels S, De Backer P, Nauwynck H. In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet.. Vet Microbiol 2007 May 16;122(1-2):43-51.
              pubmed: 17276631doi: 10.1016/j.vetmic.2007.01.004google scholar: lookup
            11. Gilkerson JR, Love DN, Drummer HE, Studdert MJ, Whalley JM. Seroprevalence of equine herpesvirus 1 in thoroughbred foals before and after weaning.. Aust Vet J 1998 Oct;76(10):677-82.
            12. Goodman LB, Loregian A, Perkins GA, Nugent J, Buckles EL, Mercorelli B, Kydd JH, Palù G, Smith KC, Osterrieder N, Davis-Poynter N. A point mutation in a herpesvirus polymerase determines neuropathogenicity.. PLoS Pathog 2007 Nov;3(11):e160.
            13. Goodman LB, Wagner B, Flaminio MJ, Sussman KH, Metzger SM, Holland R, Osterrieder N. Comparison of the efficacy of inactivated combination and modified-live virus vaccines against challenge infection with neuropathogenic equine herpesvirus type 1 (EHV-1).. Vaccine 2006 Apr 24;24(17):3636-45.
              pubmed: 16513225doi: 10.1016/j.vaccine.2006.01.062google scholar: lookup
            14. Haasnoot J, Westerhout EM, Berkhout B. RNA interference against viruses: strike and counterstrike.. Nat Biotechnol 2007 Dec;25(12):1435-43.
              pmc: PMC7096910pubmed: 18066040doi: 10.1038/nbt1369google scholar: lookup
            15. Harless W, Pusterla N. Equine herpesvirus 1 and 4 respiratory disease in the horse. Clinical Techniques in Equine Practice 2006;5:197–202.
            16. Heinrich A, Riethmüller D, Gloger M, Schusser GF, Giese M, Ulbert S. RNA interference protects horse cells in vitro from infection with Equine Arteritis Virus.. Antiviral Res 2009 Mar;81(3):209-16.
            17. Henninger RW, Reed SM, Saville WJ, Allen GP, Hass GF, Kohn CW, Sofaly C. Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center.. J Vet Intern Med 2007 Jan-Feb;21(1):157-65.
            18. Jarosinski KW, Yunis R, O'Connell PH, Markowski-Grimsrud CJ, Schat KA. Influence of genetic resistance of the chicken and virulence of Marek's disease virus (MDV) on nitric oxide responses after MDV infection.. Avian Dis 2002 Jul-Sep;46(3):636-49.
            19. Li BJ, Tang Q, Cheng D, Qin C, Xie FY, Wei Q, Xu J, Liu Y, Zheng BJ, Woodle MC, Zhong N, Lu PY. Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque.. Nat Med 2005 Sep;11(9):944-51.
              pmc: PMC7095788pubmed: 16116432doi: 10.1038/nm1280google scholar: lookup
            20. Maxwell LK, Bentz BG, Bourne DW, Erkert RS. Pharmacokinetics of valacyclovir in the adult horse.. J Vet Pharmacol Ther 2008 Aug;31(4):312-20.
            21. Nugent J, Birch-Machin I, Smith KC, Mumford JA, Swann Z, Newton JR, Bowden RJ, Allen GP, Davis-Poynter N. Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic disease outbreaks.. J Virol 2006 Apr;80(8):4047-60.
            22. O'Brien L. Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs.. Antiviral Res 2007 Jul;75(1):20-9.
            23. Patel JR, Bateman H, Williams J, Didlick S. Derivation and characterisation of a live equid herpes virus-1 (EHV-1) vaccine to protect against abortion and respiratory disease due to EHV-1.. Vet Microbiol 2003 Jan 2;91(1):23-39.
              pubmed: 12441229doi: 10.1016/s0378-1135(02)00259-6google scholar: lookup
            24. Perkins GA, Goodman LB, Dubovi EJ, Kim SG, Osterrieder N. Detection of equine herpesvirus-1 in nasal swabs of horses by quantitative real-time PCR.. J Vet Intern Med 2008 Sep-Oct;22(5):1234-8.
            25. Slater JD, Borchers K, Thackray AM, Field HJ. The trigeminal ganglion is a location for equine herpesvirus 1 latency and reactivation in the horse.. J Gen Virol 1994 Aug;75 ( Pt 8):2007-16.
              pubmed: 8046404doi: 10.1099/0022-1317-75-8-2007google scholar: lookup
            26. Stassen L, Huismans H, Theron J. Silencing of African horse sickness virus VP7 protein expression in cultured cells by RNA interference.. Virus Genes 2007 Dec;35(3):777-83.
              pubmed: 17851744doi: 10.1007/s11262-007-0162-4google scholar: lookup
            27. Stevenson M. Therapeutic potential of RNA interference.. N Engl J Med 2004 Oct 21;351(17):1772-7.
              pubmed: 15496626doi: 10.1056/nejmra045004google scholar: lookup
            28. Van de Walle GR, Goupil R, Wishon C, Damiani A, Perkins GA, Osterrieder N. A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease.. J Infect Dis 2009 Jul 1;200(1):20-5.
              pubmed: 19456260doi: 10.1086/599316google scholar: lookup
            29. van der Meulen KM, Favoreel HW, Pensaert MB, Nauwynck HJ. Immune escape of equine herpesvirus 1 and other herpesviruses of veterinary importance.. Vet Immunol Immunopathol 2006 May 15;111(1-2):31-40.
              pubmed: 16472872doi: 10.1016/j.vetimm.2006.01.006google scholar: lookup

            Citations

            This article has been cited 1 times.
            1. Schnabel CL, Wimer CL, Perkins G, Babasyan S, Freer H, Watts C, Rollins A, Osterrieder N, Wagner B. Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity.. BMC Vet Res 2018 Aug 22;14(1):245.
              doi: 10.1186/s12917-018-1563-4pubmed: 30134896google scholar: lookup