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Virology2003; 313(2); 537-552; doi: 10.1016/s0042-6822(03)00344-1

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.

Abstract: Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined.
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Publication Date: 2003-09-05 PubMed ID: 12954220PubMed Central: PMC3342690DOI: 10.1016/s0042-6822(03)00344-1Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

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.

This research investigates how the specific targets of certain immune responses in horses infected with a virus called Equine Infectious Anemia Virus (EIAV) may be linked with the severity of the disease and amount of virus present.

Background

  • The research focuses on EIAV, a lentivirus reminiscent of human HIV, leading to enduring infections in horses.
  • Cytotoxic T lymphocytes (CTLs) are a type of immune cell important in eliminating infections. The researchers considered that CTLs with solid binding (high avidity) to reliable, unchanging viral components (nonvariable epitopes) might be associated with minor infection and less severe disease.

Study Design and Hypothesis

  • They conducted a comparative study involving two groups of EIAV infected horses identified as progressors and nonprogressors.
  • Progressors are horses with elevated viral counts in their bloodstream and recurring illness, while nonprogressors are horses that maintain low-invisible levels of virus and experience mild disease.

Findings

  • In a horse classified as progressor, the researchers observed that high-avidity memory CTLs, ones that had previously encountered and remembered the virus, recognized a specific EIAV component (an envelope gp90 epitope).
  • This is the first recorded instance where variation in EIAV has led to escape from the CTLs’ immunity – that is, the virus alters to evade being recognized and targeted by CTLs.
  • In contrast, both nonprogressors had high-to-moderate avidity memory CTLs that targeted structures within a distinct viral protein (Rev) involved in viral replication, specifically the nuclear export and nuclear localization areas.

Interpretation

  • This data suggests that what the CTLs target (epitope specificity) is significant in determining how severe the disease becomes in horses infected with EIAV.
  • Nonprogressor horses had CTLs that targeted structures integral to the viral replication machinery which could contribute to their ability to control viral load and mild disease manifestation.
  • However, as the virus evolved in the progressor horse to escape recognition, this could have led to higher viral loads and more severe disease.

Cite This Article

APA
Mealey RH, Zhang B, Leib SR, Littke MH, McGuire TC. (2003). 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, 313(2), 537-552. https://doi.org/10.1016/s0042-6822(03)00344-1

Publication

Virology
ISSN: 0042-6822
NlmUniqueID: 0110674
Country: United States
Language: English
Volume: 313
Issue: 2
Pages: 537-552

Researcher Affiliations

Mealey, Robert H
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. rhm@vetmed.wsu.edu
Zhang, Baoshan
    Leib, Steven R
      Littke, Matt H
        McGuire, Travis C

          MeSH Terms

          • Amino Acid Sequence
          • Animals
          • Disease Progression
          • Epitope Mapping
          • Epitopes, T-Lymphocyte / immunology
          • Equine Infectious Anemia / diagnosis
          • Equine Infectious Anemia / immunology
          • Equine Infectious Anemia / virology
          • Fever / veterinary
          • Glycoproteins / genetics
          • Glycoproteins / immunology
          • Horses
          • Immunologic Memory
          • Infectious Anemia Virus, Equine / chemistry
          • Molecular Sequence Data
          • RNA, Viral / analysis
          • Sequence Alignment
          • T-Lymphocytes, Cytotoxic / immunology
          • Thrombocytopenia / veterinary
          • Viral Envelope Proteins / genetics
          • Viral Envelope Proteins / immunology
          • Viral Load / veterinary

          Grant Funding

          • K08 AI001575 / NIAID NIH HHS
          • AI01575 / NIAID NIH HHS
          • AI24291 / NIAID NIH HHS

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