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The Journal of general virology2007; 88(Pt 4); 1324-1336; doi: 10.1099/vir.0.82391-0

Envelope-specific T-helper and cytotoxic T-lymphocyte responses associated with protective immunity to equine infectious anemia virus.

Abstract: Equine infectious anemia virus (EIAV) infection of horses provides a valuable model for examining the natural immunological control of lentivirus infection and disease and the mechanisms of protective and enhancing vaccine immunity. We have previously hypothesized that the EIAV envelope (Env) proteins gp90 and gp45 are major determinants of vaccine efficacy, and that the development of protective immunity by attenuated viral vaccines may be associated with the progressive redirection of immune responses from immunodominant, variable Env segments to immunorecessive, conserved Env sequences. Whilst the antibody-neutralization determinants of Env have been defined, there are to date no comprehensive analyses of the lymphoproliferative (T-helper, Th) and cytotoxic T-cell (CTL) epitopes of the EIAV Env proteins. Thus, in the current study, synthetic-peptide methodologies were used to define regions of EIAV Env associated with protective vaccine immunity in a panel of 12 horses inoculated with the attenuated EIAV(D9) vaccine and two asymptomatic carrier horses infected experimentally with the virulent EIAV(PV) strain expressing the same Env protein as the vaccine strain. The results of these studies identified 17 broadly reactive Th peptides and six broadly reactive CTL peptides in the Env proteins of EIAV that were associated with protective immunity. Thus, these data provide for the first time a comprehensive mapping of EIAV Env-specific cellular regions that can be used to examine the development of protective immunity and to evaluate potential cellular immune determinants of protective immunity.
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Publication Date: 2007-03-22 PubMed ID: 17374779DOI: 10.1099/vir.0.82391-0Google 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 research article focuses on the study of the equine infectious anemia virus (EIAV), more specifically the significance of the envelope proteins (Env) in the development of protective immunity to this virus. The researchers identified certain peptides in the Env that were tied to protective immunity.

Significance of the Study

  • The study offers significant value as it sheds light on the role and importance of envelope proteins in protective immunity against a highly infectious disease like EIAV in horses.
  • This research provides a comprehensive mapping of EIAV envelope-specific cellular regions for the very first time. This information can be used in the future to examine the development of protective immunity and also to evaluate potential immune determinants of protective immunity.

Research Hypothesis and Methodology

  • The authors hypothesized that the EIAV envelope proteins, known as gp90 and gp45, might be the key factors determining vaccine efficacy.
  • They suggested the progressive redirection of immune responses from dominant, variable envelope segments to recessive, conserved envelope sequences might develop protective immunity.
  • The researchers used synthetic-peptide methodologies to define regions of EIAV envelope associated with protective vaccine immunity in a panel of 12 horses inoculated with the attenuated EIAV(D9) vaccine and two asymptomatic carrier horses infected experimentally with the virulent EIAV(PV) strain expressing the same envelope proteins as the vaccine strain.

Research Findings

  • The authors identified 17 broadly reactive T-helper peptides and six broadly reactive cytotoxic T-cell peptides in the EIAV envelope proteins associated with protective immunity.
  • While the antibody-neutralizing determinants of Env have been defined, this is the first comprehensive analyses of the lymphoproliferative (T-helper, Th) and cytotoxic T-cell (CTL) epitopes of the EIAV envelope proteins.
  • These findings pave the way for a deeper understanding of how protective immunity is developed and can shape future research in EIAV as well as other lentiviruses.

Cite This Article

APA
Tagmyer TL, Craigo JK, Cook SJ, Issel CJ, Montelaro RC. (2007). Envelope-specific T-helper and cytotoxic T-lymphocyte responses associated with protective immunity to equine infectious anemia virus. J Gen Virol, 88(Pt 4), 1324-1336. https://doi.org/10.1099/vir.0.82391-0

Publication

The Journal of general virology
ISSN: 0022-1317
NlmUniqueID: 0077340
Country: England
Language: English
Volume: 88
Issue: Pt 4
Pages: 1324-1336

Researcher Affiliations

Tagmyer, Tara L
  • Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Molecular Virology and Microbiology Graduate Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Craigo, Jodi K
  • Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Cook, Sheila J
  • Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY 40516, USA.
Issel, Charles J
  • Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY 40516, USA.
Montelaro, Ronald C
  • Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

MeSH Terms

  • Animals
  • Cell Proliferation
  • Cytotoxicity Tests, Immunologic
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology
  • Equine Infectious Anemia / immunology
  • Horses
  • Infectious Anemia Virus, Equine / immunology
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Helper-Inducer / immunology
  • Viral Envelope Proteins / immunology
  • Viral Vaccines / immunology

Grant Funding

  • R01 AI25850 / NIAID NIH HHS

Citations

This article has been cited 10 times.
  1. Craigo JK, Ezzelarab C, Cook SJ, Liu C, Horohov D, Issel CJ, Montelaro RC. Protective efficacy of centralized and polyvalent envelope immunogens in an attenuated equine lentivirus vaccine. PLoS Pathog 2015 Jan;11(1):e1004610.
    doi: 10.1371/journal.ppat.1004610pubmed: 25569288google scholar: lookup
  2. Liu C, Cook SJ, Craigo JK, Cook FR, Issel CJ, Montelaro RC, Horohov DW. Epitope shifting of gp90-specific cellular immune responses in EIAV-infected ponies. Vet Immunol Immunopathol 2014 Oct 15;161(3-4):161-9.
    doi: 10.1016/j.vetimm.2014.08.001pubmed: 25176006google scholar: lookup
  3. Craigo JK, Montelaro RC. Lessons in AIDS vaccine development learned from studies of equine infectious, anemia virus infection and immunity. Viruses 2013 Dec 2;5(12):2963-76.
    doi: 10.3390/v5122963pubmed: 24316675google scholar: lookup
  4. Craigo JK, Ezzelarab C, Cook SJ, Chong L, Horohov D, Issel CJ, Montelaro RC. Envelope determinants of equine lentiviral vaccine protection. PLoS One 2013;8(6):e66093.
    doi: 10.1371/journal.pone.0066093pubmed: 23785473google scholar: lookup
  5. Liu C, Cook FR, Cook SJ, Craigo JK, Even DL, Issel CJ, Montelaro RC, Horohov DW. The determination of in vivo envelope-specific cell-mediated immune responses in equine infectious anemia virus-infected ponies. Vet Immunol Immunopathol 2012 Aug 15;148(3-4):302-10.
    doi: 10.1016/j.vetimm.2012.06.018pubmed: 22795699google scholar: lookup
  6. Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Wang F, Shen R, Zhou J. Unique evolution characteristics of the envelope protein of EIAV(LN₄₀), a virulent strain of equine infectious anemia virus. Virus Genes 2011 Apr;42(2):220-8.
    doi: 10.1007/s11262-010-0563-7pubmed: 21369830google scholar: lookup
  7. Craigo JK, Barnes S, Cook SJ, Issel CJ, Montelaro RC. Divergence, not diversity of an attenuated equine lentivirus vaccine strain correlates with protection from disease. Vaccine 2010 Nov 29;28(51):8095-104.
    doi: 10.1016/j.vaccine.2010.10.003pubmed: 20955830google scholar: lookup
  8. Craigo JK, Barnes S, Zhang B, Cook SJ, Howe L, Issel CJ, Montelaro RC. An EIAV field isolate reveals much higher levels of subtype variability than currently reported for the equine lentivirus family. Retrovirology 2009 Oct 20;6:95.
    doi: 10.1186/1742-4690-6-95pubmed: 19843328google scholar: lookup
  9. Tagmyer TL, Craigo JK, Cook SJ, Even DL, Issel CJ, Montelaro RC. Envelope determinants of equine infectious anemia virus vaccine protection and the effects of sequence variation on immune recognition. J Virol 2008 Apr;82(8):4052-63.
    doi: 10.1128/JVI.02028-07pubmed: 18234792google scholar: lookup
  10. Craigo JK, Zhang B, Barnes S, Tagmyer TL, Cook SJ, Issel CJ, Montelaro RC. Envelope variation as a primary determinant of lentiviral vaccine efficacy. Proc Natl Acad Sci U S A 2007 Sep 18;104(38):15105-10.
    doi: 10.1073/pnas.0706449104pubmed: 17846425google scholar: lookup
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