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Home / Equine Research Bank / J Virol / Adaptive immunity is the primary force driving selection of ...
Journal of virology2004; 78(17); 9295-9305; doi: 10.1128/JVI.78.17.9295-9305.2004

Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection.

Abstract: Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infection in horses. The appearance of antigenically distinct viral variants during recurrent viremic episodes is thought to be due to adaptive immune selection pressure. To test this hypothesis, we evaluated envelope SU cloned sequences from five severe combined immunodeficient (SCID) foals infected with EIAV. Within the SU hypervariable V3 region, 8.5% of the clones had amino acid changes, and 6.4% had amino acid changes within the known cytotoxic T lymphocyte (CTL) epitope Env-RW12. Of all the SU clones, only 3.1% had amino acid changes affecting potential N-linked glycosylation sites. In contrast, a much higher degree of variation was evident in SU sequences obtained from four EIAV-infected immunocompetent foals. Within V3, 68.8% of the clones contained amino acid changes, and 50% of the clones had amino acid changes within the Env-RW12 CTL epitope. Notably, 31.9% of the clones had amino acid changes affecting one or more glycosylation sites. Marked amino acid variation occurred in cloned SU sequences from an immune-reconstituted EIAV-infected SCID foal. Of these clones, 100% had amino acid changes within V3, 100% had amino acid changes within Env-RW12, and 97.5% had amino acid changes affecting glycosylation sites. Analysis of synonymous and nonsynonymous nucleotide substitutions revealed statistically significant differences between SCID and immunocompetent foals and between SCID foals and the reconstituted SCID foal. Interestingly, amino acid selection at one site occurred independently of adaptive immune status. Not only do these data indicate that adaptive immunity primarily drives the selection of EIAV SU variants, but also they demonstrate that other selective forces exist during acute infection.
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Publication Date: 2004-08-17 PubMed ID: 15308724PubMed Central: PMC506964DOI: 10.1128/JVI.78.17.9295-9305.2004Google 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.

This study explores the role of adaptive immunity in dictating the selection of variants of the equine infectious anemia virus (EIAV). The findings indicate that adaptive immune responses are the primary influencers of the variant selection, but also suggest that other selection pressures exist during acute infection.

Research Overview

The research establishes the role of the adaptive immunity in determining the selection of equine infectious anemia virus (EIAV) variant during the acute phase of infection. The exploration is based on the appearance of antigenically distinct viral variants observed during recurrent viremic episodes, hypothesized to be the result of adaptive immune selection pressure.

Methodology

  • The researchers used cloned sequences from the SU envelope of the EIAV derived from five SCID (Severe Combined Immunodeficient) foals.
  • The primary sites for comparison were the V3 region and a known cytotoxic T lymphocyte (CTL) epitope Env-RW12, both within the SU hypervariable region. The researchers focused on changes in the amino acid sequence, which indicate biological variation.
  • The study also involved sequences from four EIAV-infected immunocompetent foals, which served as a comparison group.

    • Finally, sequences from an immune-reconstituted EIAV-infected SCID foal were also investigated, yielding information on the immune response implications on sequence variation.

Findings

  • In the SCID foals, only a minor proportion of the clones demonstrated changes in the amino acid sequence in either the V3 region or the CTL epitope.
  • In marked contrast, a significantly high degree of variation was observed in the immunocompetent foals with changes noted in the majority of clones from the V3 region, the CTL epitope, and the glycosylation sites.
  • The reconstituted SCID foal showed 100% variation within the V3 and CTL epitope, indicating a high degree of selection due to the revived immune response.
  • Although adaptive immunity was found to be the primary driver of EIAV variant selection, the study found evidence of other selective forces during acute infection.

Conclusion

The research underscores the critical role of adaptive immunity in the selection of EIAV variants during acute infection. Nonetheless, it acknowledges the potential interplay of other selective factors in driving biological variation of the virus. The understanding of these dynamics can have implications for the development of therapeutic interventions for EIAV and other similar persistent infections.

Cite This Article

APA
Mealey RH, Leib SR, Pownder SL, McGuire TC. (2004). Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection. J Virol, 78(17), 9295-9305. https://doi.org/10.1128/JVI.78.17.9295-9305.2004

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 78
Issue: 17
Pages: 9295-9305

Researcher Affiliations

Mealey, Robert H
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040, USA. rhm@vetmed.wsu.edu
Leib, Steven R
    Pownder, Sarah L
      McGuire, Travis C

        MeSH Terms

        • Acute Disease
        • Amino Acid Sequence
        • Animals
        • Antigenic Variation / genetics
        • Antigenic Variation / immunology
        • Equine Infectious Anemia / immunology
        • Equine Infectious Anemia / virology
        • Genetic Variation / genetics
        • Horse Diseases / immunology
        • Horse Diseases / virology
        • Horses / immunology
        • Horses / virology
        • Infectious Anemia Virus, Equine / genetics
        • Infectious Anemia Virus, Equine / immunology
        • Membrane Glycoproteins / chemistry
        • Membrane Glycoproteins / genetics
        • Membrane Glycoproteins / immunology
        • Molecular Sequence Data
        • Point Mutation / genetics
        • Selection, Genetic
        • Severe Combined Immunodeficiency / immunology
        • Severe Combined Immunodeficiency / veterinary
        • Severe Combined Immunodeficiency / virology
        • Viral Envelope Proteins / chemistry
        • Viral Envelope Proteins / genetics
        • Viral Envelope Proteins / immunology

        Grant Funding

        • K08 AI001575 / NIAID NIH HHS
        • AI01575 / NIAID NIH HHS
        • AI24291 / NIAID NIH HHS
        • R21 AI058787 / NIAID NIH HHS
        • AI058787 / NIAID NIH HHS

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        Citations

        This article has been cited 11 times.
        1. Ramsay JD, Evanoff R, Mealey RH. Hepacivirus A Infection in Horses Defines Distinct Envelope Hypervariable Regions and Elucidates Potential Roles of Viral Strain and Adaptive Immune Status in Determining Envelope Diversity and Infection Outcome.. J Virol 2018 Sep 15;92(18).
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