Natural variation of equine infectious anemia virus Gag protein cytotoxic T lymphocyte epitopes.
Abstract: Two defined cytotoxic T lymphocyte (CTL) epitopes from equine infectious anemia virus (EIAV)-infected horses, equine leukocyte alloantigen (ELA)-A5.1-restricted epitope 18a, and ELA-A9-restricted epitope 28b-1 were evaluated for conservation among three wild-type EIAV strains. Epitope 18a variation occurred in all three wild-type EIAV strains, while epitope 28b-1 varied in one strain. Further, 12% amino acid changes occurred in the Gag proteins of a recently isolated wild-type strain, documenting a much greater Gag protein variation than previously reported. Evaluation of epitope 18a among two virus isolates from sequential disease episodes in a single horse, H513 (ELA-A5.1/A8), demonstrated that no variation that affected CTL recognition occurred. H513 PBMC had CTLm to epitope 18a before the occurrence of disease episodes caused by viruses expressing epitope 18a; however, the frequencies were low (5-15/10(6) PBMC). Later in infection there was an absence of disease episodes associated with an increase in CTLm frequency to EIAV(WSU5)-infected targets, but not epitope 18a-pulsed targets. Therefore, if CTLm to EIAV epitopes were involved in maintaining the carrier state in H513, they recognized epitopes other than 18a.
Copyright 1999 Academic Press.
Publication Date: 1999-09-25 PubMed ID: 10497109DOI: 10.1006/viro.1999.9862Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research studied the variability of two specific epitopes (parts of an antigen recognized by the immune system) of the equine infectious anemia virus (EIAV) in different strains of the virus. It found variations in both epitopes across these strains, and also discovered a significant degree of variation in the Gag proteins of a newly-isolated strain. No variation affecting immune recognition was observed in a horse infected multiple times. The findings imply that immune recognition in this horse might involve epitopes other than the two studied in this research.
Background
- The research focuses on studying equine infectious anemia virus (EIAV), a viral disease in horses that affects their immune system and blood cells, causing symptoms such as anemia, fever, and weight loss.
- The specific components studied from the virus are the cytotoxic T lymphocyte (CTL) epitopes, regions on an antigen that are recognized by CTLs, immune cells that kill infected host cells.
- Specific attention is given to two epitopes, known as epitope 18a and epitope 28b-1, which are specific to two different horse leukocyte alloantigens (HLA), ELA-A5.1 and ELA-A9 respectively. ELA stands for Equine Leukocyte Antigen, a system of cell surface proteins involved in immune response in horses.
Findings
- The researchers found variations in both the CTL epitopes 18a and 28b-1 in three different wild strains of EIAV. This reveals that these epitopes are not universally similar or conserved in all EIAV strains.
- The research also discovered significant variations, about a 12% amino acid change, in the Gag proteins of a newly isolated strain of EIAV. The Gag protein is an essential protein for the virus, involved in virus assembly and release.
- When the team investigated epitope 18a in two virus isolates from a single horse (named H513), that had sequential disease episodes, no variation that could affect immune recognition was found.
- They also noted changes in the horse’s immunity over time in relation to epitope 18a, with immune responses being present before and absence of disease episodes later associated with an increased immune response, though not to epitope 18a.
Implications
- The findings of the research suggest that there is a level of variability in the epitopes of the EIAV virus across different strains, which could have implications for vaccine development.
- The lack of variation in epitope 18a in a single horse over the course of infection and disease suggests that this epitope may not be the primary target of the immune system for EIAV in this context.
- The increased immune response noted in the later infection stages in the horse, despite not being directed at epitope 18a, potentially represents recognition of other unaffected epitopes, implying the immune system can maintain the carrier state by recognizing multiple epitopes.
Cite This Article
APA
Zhang W, Auyong DB, Oaks JL, McGuire TC.
(1999).
Natural variation of equine infectious anemia virus Gag protein cytotoxic T lymphocyte epitopes.
Virology, 261(2), 242-252.
https://doi.org/10.1006/viro.1999.9862 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040, USA.
MeSH Terms
- Amino Acid Sequence
- Animals
- Antigen Presentation
- Antigenic Variation
- Antigens, Viral / genetics
- Antigens, Viral / immunology
- Epitopes / immunology
- Equine Infectious Anemia / immunology
- Gene Products, gag / genetics
- Gene Products, gag / immunology
- Horses
- Infectious Anemia Virus, Equine / immunology
- Molecular Sequence Data
- T-Lymphocytes, Cytotoxic / immunology
Grant Funding
- AI-01255 / NIAID NIH HHS
- AI-24291 / NIAID NIH HHS
Citations
This article has been cited 7 times.- 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.
- Taylor SD, Leib SR, Carpenter S, Mealey RH. Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses.. J Virol 2010 Jul;84(13):6536-48.
- 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.
- Chung C, Mealey RH, McGuire TC. CTL from EIAV carrier horses with diverse MHC class I alleles recognize epitope clusters in Gag matrix and capsid proteins.. Virology 2004 Sep 15;327(1):144-54.
- 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.
- Fraser DG, Oaks JL, Brown WC, McGuire TC. Identification of broadly recognized, T helper 1 lymphocyte epitopes in an equine lentivirus.. Immunology 2002 Mar;105(3):295-305.
- Mealey RH, Fraser DG, Oaks JL, Cantor GH, McGuire TC. Immune reconstitution prevents continuous equine infectious anemia virus replication in an Arabian foal with severe combined immunodeficiency: lessons for control of lentiviruses.. Clin Immunol 2001 Nov;101(2):237-47.
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