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Journal of virology1999; 73(4); 2762-2769; doi: 10.1128/JVI.73.4.2762-2769.1999

Detection and induction of equine infectious anemia virus-specific cytotoxic T-lymphocyte responses by use of recombinant retroviral vectors.

Abstract: Cytotoxic T lymphocytes (CTL) appear to be critical in resolving or reducing the severity of lentivirus infections. Retroviral vectors expressing the Gag/Pr or SU protein of the lentivirus equine infectious anemia virus (EIAV) were constructed and used to evaluate EIAV-specific CTL responses in horses. Three promoters, cytomegalovirus, simian virus SV40, and Moloney murine sarcoma virus (MoMSV) long terminal repeat (LTR), were used, and there was considerable variation in their ability to direct expression of Gag/Pr and SU. Vectors expressing EIAV proteins under the direction of MoMSV LTR and using the gibbon ape leukemia virus (GALV) Env for internalization were efficient at transducing equine kidney (EK) target cells and were effective targets for EIAV-specific CTL lysis. CTL from EIAV-infected horses caused lysis of retroviral vector-transduced EK cells expressing either Gag/Pr or SU in an ELA-A-restricted manner. In contrast, lysis of recombinant vaccinia virus-infected EK cells expressing Gag/Pr and SU/TM was often non-LA-A restricted. Five horses were immunized by direct intramuscular injection with a mixture of retroviral vectors expressing Gag/Pr or SU, and one responded with EIAV-specific CTL. This result indicates that retroviral vector stimulation of CTL in horses needs to be optimized, perhaps by inclusion of appropriate cytokine genes in the constructs. However, the studies demonstrated that retroviral vector-transduced target cells were very effective for in vitro dissection of EIAV-specific CTL responses.
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Publication Date: 1999-03-12 PubMed ID: 10074123PubMed Central: PMC104033DOI: 10.1128/JVI.73.4.2762-2769.1999Google Scholar: Lookup
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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 discusses the effectiveness of retroviral vectors in invoking and studying the specific immune response of horses against the Equine Infectious Anemia Virus (EIAV). The study also investigates the potential optimization of this process by using cytokine genes.

Introduction to the Study

  • The study seeks to understand the role of Cytotoxic T lymphocytes (CTL) in combating lentivirus infections, a group of viruses which includes the Equine Infectious Anemia Virus (EIAV).
  • The researchers constructed retroviral vectors, which are components that carry and replicate genetic material within a host cell, expressing either the Gag/Pr, or SU proteins of EIAV.
  • These vectors are utilized to evaluate the specific immune response of horses to EIAV.

Investigational Approach and Variation

  • Three different promoters were used in the study: cytomegalovirus, simian virus SV40, and Moloney murine sarcoma virus (MoMSV) long terminal repeat (LTR).
  • A significant variation was observed in their capacities to guide the expression of the Gag/Pr and SU proteins.
  • Vectors which expressed EIAV proteins, under the control of MoMSV LTR, and using the Gibbon ape leukemia virus (GALV) Env for internalization, were efficient at transducing equine kidney (EK) target cells.

Significance of CTL Lysis and EIAV-Specific Immune Responses

  • CTL from EIAV infected horses caused the destruction of the retroviral vector transduced EK cells, which expressed either Gag/Pr or SU, in an Equine Lymphocyte Antigen-A (ELA-A) restricted manner.
  • This proves that the immune response was specific to EIAV as the lysis occurred only when specific antigens, expressed by the virus, were present.
  • The lysis of recombinant vaccinia virus infected EK cells expressing Gag/Pr and SU/TM was often not restricted to ELA-A, shedding light on the different immune responses triggered by these pathogen expressions.

Immunization Trial and Further Optimization

  • Five horses were immunized with a mixture of retroviral vectors expressing either Gag/Pr or SU proteins.
  • Only one horse responded with EIAV-specific CTL, signaling that the procedure of retroviral vector stimulation of CTL in horses needs further optimization.
  • Potential optimization methods could include the addition of appropriate cytokine genes in the construct.
  • This study underlines the effectiveness of retroviral vector-transduced target cells for the in vitro study of EIAV-specific CTL responses.

Cite This Article

APA
Lonning SM, Zhang W, Leib SR, McGuire TC. (1999). Detection and induction of equine infectious anemia virus-specific cytotoxic T-lymphocyte responses by use of recombinant retroviral vectors. J Virol, 73(4), 2762-2769. https://doi.org/10.1128/JVI.73.4.2762-2769.1999

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 73
Issue: 4
Pages: 2762-2769

Researcher Affiliations

Lonning, S M
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164, USA.
Zhang, W
    Leib, S R
      McGuire, T C

        MeSH Terms

        • Animals
        • Antigens, Viral / immunology
        • DNA, Recombinant / immunology
        • Equine Infectious Anemia / immunology
        • Gene Products, gag / immunology
        • Genetic Vectors / immunology
        • Glycoproteins / immunology
        • Horses / immunology
        • Horses / virology
        • Infectious Anemia Virus, Equine / genetics
        • Infectious Anemia Virus, Equine / immunology
        • Lymphocyte Activation
        • Sarcoma Viruses, Murine / genetics
        • Sarcoma Viruses, Murine / immunology
        • T-Lymphocytes, Cytotoxic / immunology
        • Viral Envelope Proteins / immunology
        • Viral Vaccines

        Grant Funding

        • AI01260 / NIAID NIH HHS
        • AI24291 / NIAID NIH HHS

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        Citations

        This article has been cited 7 times.
        1. Mealey RH, Leib SR, Littke MH, Wagner B, Horohov DW, McGuire TC. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen.. Vaccine 2009 Apr 21;27(18):2453-68.
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        2. Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: lack of correlation between in vitro activity and in vivo efficacy.. Vet Immunol Immunopathol 2008 Jan 15;121(1-2):8-22.
          doi: 10.1016/j.vetimm.2007.07.011pubmed: 17727961google scholar: lookup
        3. Mealey RH, Lee JH, Leib SR, Littke MH, McGuire TC. A single amino acid difference within the alpha-2 domain of two naturally occurring equine MHC class I molecules alters the recognition of Gag and Rev epitopes by equine infectious anemia virus-specific CTL.. J Immunol 2006 Nov 15;177(10):7377-90.
          doi: 10.4049/jimmunol.177.10.7377pubmed: 17082657google scholar: lookup
        4. Mealey RH, Sharif A, Ellis SA, Littke MH, Leib SR, McGuire TC. Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes.. Virology 2005 Aug 15;339(1):110-26.
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        5. Mealey RH, Zhang B, Leib SR, Littke MH, McGuire TC. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus.. Virology 2003 Sep 1;313(2):537-52.
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