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Veterinary microbiology2011; 157(1-2); 220-225; doi: 10.1016/j.vetmic.2011.11.031

Assessment of correlation between in vitro CD3+ T cell susceptibility to EAV infection and clinical outcome following experimental infection.

Abstract: In a recent study, we demonstrated that the virulent Bucyrus strain (VBS) of EAV could infect in vitro a small population of CD3(+) T lymphocytes from some but not all horses. Furthermore, we have shown that a common haplotype is associated with this in vitro CD3(+) T cell susceptibility/resistance phenotype to EAV infection. In this study, we investigated whether the differences in the susceptibility or resistance of CD3(+) T cells in vitro correlate with the outcome and severity of clinical signs in vivo. Thus, horses were divided into two groups based on their CD3(+) T cell susceptible or resistant phenotype. Following experimental inoculation with the recombinant VBS of EAV, horses were assessed for presence and severity of clinical signs, duration and magnitude of virus shedding, as well as production of proinflammatory and immunomodulatory cytokines in peripheral blood mononuclear cells using real-time quantitative RT-PCR. The data showed that there was a significant difference between the two groups of horses in terms of cytokine mRNA expression and evidence of increased clinical signs in horses possessing the in vitro CD3(+) T cell resistant phenotype. This is the first study to provide direct evidence for a correlation between variation in host genotype and phenotypic differences in terms of the extent of viral replication, presence and severity of clinical signs and cytokine gene expression caused by infection with virulent EAV.
Publication Date: 2011-12-02 PubMed ID: 22177968DOI: 10.1016/j.vetmic.2011.11.031Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research focuses on analysing the correlation between a horse’s susceptibility to Equine Arteritis Virus (EAV) infection in vitro and the severity of clinical signs when infected in vivo. It found that horses with a particular haplotype, associated with in vitro CD3(+) T cell resistance to EAV, showed significantly increased clinical signs of disease.

Study Objective and Methodology

  • This research sought to explore whether the differences in resistance or susceptibility of a particular type of horse’s immune cells (CD3(+) T cells) to EAV relate to the outcome and severity of clinical signs exhibited by the infected horses. The focus was on the differences in in vitro (outside the body) infection susceptibility.
  • Horses were classified into two separate groups based on their CD3(+) T cells’ in vitro susceptibility or resistance phenotype. This genetic phenotype was determined through testing the horses’ cells with the virulent Bucyrus strain (VBS) of EAV.

Experimental Procedure and Assessment

  • Following classification, the horses were experimentally infected with a recombinant version of the VBS strain of EAV.
  • The horses were then evaluated in terms of the presence and severity of clinical symptoms, duration of virus shedding (extent to which they spread the virus), and intensity of viral shedding.
  • Additionally, the production of inflammation-inducing (proinflammatory) and immune response-modifying (immunomodulatory) chemical compounds (cytokines) was examined in the horses’ blood cells. This was done utilizing real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR), a laboratory technique used to measure the amount of specific RNA (in this case, mRNA for cytokines).

Outcomes and Conclusion

  • The results showed a significant difference between the groups of horses based on cytokine mRNA expression and the severity of illness. There was particularly strong evidence of heightened clinical signs in the horses identified as being CD3(+) T cell resistant in vitro.
  • This is the first study that presents direct evidence of a correlation between differences in host genotype (specific genetic characteristics) and the severity of clinical signs, viral replication extent, and cytokine gene expression induced by the virulent strain of EAV.
  • The findings suggest that the horse’s CD3(+) T cell resistance or susceptibility could predict severity of EAV clinical signs. This information may be relevant in developing more effective treatments and preventive strategies for EAV.

Cite This Article

APA
Go YY, Cook RF, Fulgêncio JQ, Campos JR, Henney P, Timoney PJ, Horohov DW, Balasuriya UB. (2011). Assessment of correlation between in vitro CD3+ T cell susceptibility to EAV infection and clinical outcome following experimental infection. Vet Microbiol, 157(1-2), 220-225. https://doi.org/10.1016/j.vetmic.2011.11.031

Publication

ISSN: 1873-2542
NlmUniqueID: 7705469
Country: Netherlands
Language: English
Volume: 157
Issue: 1-2
Pages: 220-225

Researcher Affiliations

Go, Yun Young
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Cook, R Frank
    Fulgêncio, Juliana Q
      Campos, Juliana R
        Henney, Pamela
          Timoney, Peter J
            Horohov, David W
              Balasuriya, Udeni B R

                MeSH Terms

                • Animals
                • Arterivirus Infections / genetics
                • Arterivirus Infections / immunology
                • Arterivirus Infections / veterinary
                • CD3 Complex / genetics
                • CD3 Complex / immunology
                • Cytokines / genetics
                • Cytokines / immunology
                • Disease Susceptibility
                • Equartevirus / immunology
                • Equartevirus / pathogenicity
                • Female
                • Haplotypes
                • Horse Diseases / genetics
                • Horse Diseases / immunology
                • Horse Diseases / virology
                • Horses / immunology
                • Horses / virology
                • Immunity, Innate / genetics
                • Leukocytes, Mononuclear / immunology
                • Lymphocyte Count
                • Phenotype
                • T-Lymphocytes / immunology
                • Virus Shedding

                Citations

                This article has been cited 9 times.
                1. Thieulent CJ, Carossino M, Balasuriya UBR, Graves K, Bailey E, Eberth J, Canisso IF, Andrews FM, Keowen ML, Go YY. Development of a TaqMan(®) Allelic Discrimination qPCR Assay for Rapid Detection of Equine CXCL16 Allelic Variants Associated With the Establishment of Long-Term Equine Arteritis Virus Carrier State in Stallions. Front Genet 2022;13:871875.
                  doi: 10.3389/fgene.2022.871875pubmed: 35495124google scholar: lookup
                2. Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Cook RF, Timoney PJ, Balasuriya UBR. Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis. PLoS Pathog 2019 Jul;15(7):e1007950.
                  doi: 10.1371/journal.ppat.1007950pubmed: 31356622google scholar: lookup
                3. Nam B, Mekuria Z, Carossino M, Li G, Zheng Y, Zhang J, Cook RF, Shuck KM, Campos JR, Squires EL, Troedsson MHT, Timoney PJ, Balasuriya UBR. Intrahost Selection Pressure Drives Equine Arteritis Virus Evolution during Persistent Infection in the Stallion Reproductive Tract. J Virol 2019 Jun 15;93(12).
                  doi: 10.1128/JVI.00045-19pubmed: 30918077google scholar: lookup
                4. Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Shuck KM, Timoney PJ, Cook RF, Balasuriya UBR. Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus. J Virol 2018 May 1;92(9).
                  doi: 10.1128/JVI.00015-18pubmed: 29444949google scholar: lookup
                5. Carossino M, Loynachan AT, Canisso IF, Cook RF, Campos JR, Nam B, Go YY, Squires EL, Troedsson MHT, Swerczek T, Del Piero F, Bailey E, Timoney PJ, Balasuriya UBR. Equine Arteritis Virus Has Specific Tropism for Stromal Cells and CD8(+) T and CD21(+) B Lymphocytes but Not for Glandular Epithelium at the Primary Site of Persistent Infection in the Stallion Reproductive Tract. J Virol 2017 Jul 1;91(13).
                  doi: 10.1128/JVI.00418-17pubmed: 28424285google scholar: lookup
                6. Sarkar S, Bailey E, Go YY, Cook RF, Kalbfleisch T, Eberth J, Chelvarajan RL, Shuck KM, Artiushin S, Timoney PJ, Balasuriya UB. Allelic Variation in CXCL16 Determines CD3+ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion. PLoS Genet 2016 Dec;12(12):e1006467.
                  doi: 10.1371/journal.pgen.1006467pubmed: 27930647google scholar: lookup
                7. Go YY, Li Y, Chen Z, Han M, Yoo D, Fang Y, Balasuriya UB. Equine arteritis virus does not induce interferon production in equine endothelial cells: identification of nonstructural protein 1 as a main interferon antagonist. Biomed Res Int 2014;2014:420658.
                  doi: 10.1155/2014/420658pubmed: 24967365google scholar: lookup
                8. Balasuriya UB, Zhang J, Go YY, MacLachlan NJ. Experiences with infectious cDNA clones of equine arteritis virus: lessons learned and insights gained. Virology 2014 Aug;462-463:388-403.
                  doi: 10.1016/j.virol.2014.04.029pubmed: 24913633google scholar: lookup
                9. Balasuriya UB, Go YY, MacLachlan NJ. Equine arteritis virus. Vet Microbiol 2013 Nov 29;167(1-2):93-122.
                  doi: 10.1016/j.vetmic.2013.06.015pubmed: 23891306google scholar: lookup