Antibody reactions of horses against various domains of the EHV-1 receptor-binding protein gD1.
Abstract: Equid alphaherpesviruses 1 (EHV-1) and 4 (EHV-4) are closely related and both endemic in horses worldwide. Both viruses replicate in the upper respiratory tract, but EHV-1 may additionally lead to abortion and equine herpesvirus myeloencephalopathy (EHM). We focused on antibody responses in horses against the receptor-binding glycoprotein D of EHV-1 (gD1), which shares a 77% amino acid identity with its counterpart in EHV-4 (gD4). Both antigens give rise to cross-reacting antibodies, including neutralizing antibodies. However, immunity against EHV-4 is not considered protective against EHM. While a diagnostic ELISA to discriminate between EHV-1 and EHV-4 infections is available based on type-specific fragments of glycoprotein G (gG1 and gG4, respectively), the type-specific antibody reaction against gD1 has not yet been sufficiently addressed. Starting from the N-terminus of gD1, we developed luciferase immunoprecipitation system (LIPS) assays, using gD1-fragments of increasing size as antigens, i.e. gD1_83 (comprising the first 83 amino acids), gD1_160, gD1_180, and gD1_402 (the full-length molecule). These assays were then used to analyse panels of horse sera from Switzerland (n = 60) and Iceland (n = 50), the latter of which is considered EHV-1 free. We detected only one true negative horse serum from Iceland, whereas all other sera in both panels were seropositive for both gG4 (ELISA) and gD1 (LIPS against gD1_402). In contrast, seropositivity against gG1 was rather rare (35% Swiss sera; 14% Icelandic sera). Therefore, a high percentage of antibodies against gD1 could be attributed to cross-reaction and due to EHV-4 infections. In contrast, the gD1_83 fragment was able to identify sera with type-specific antibodies against gD1. Interestingly, those sera stemmed almost exclusively from vaccinated horses. Although it is uncertain that the N-terminal epitopes of gD1 addressed in this communication are linked to better protection, we suggest that in future vaccine developments, type-common antigens should be avoided, while a broad range of type-specific antigens should be favored.
Copyright: © 2024 Schramm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publication Date: 2024-07-12 PubMed ID: 38995916PubMed Central: PMC11244823DOI: 10.1371/journal.pone.0301987Google Scholar: Lookup
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Summary
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The research article focuses on the antibody responses in horses against a specific protein present in Equid alphaherpesviruses-1 (EHV-1). The study uses luciferase immunoprecipitation system (LIPS) assays and also discusses implications of the findings on potential vaccine developments.
Understanding the Research Background
- Equid alphaherpesviruses 1 (EHV-1) and 4 (EHV-4) are closely related viruses, which cause infections in horses globally. Both these viruses primarily replicate in the upper respiratory tract. However, EHV-1 also results sometimes in abortion and equine herpesvirus myeloencephalopathy (EHM).
- The study examines the antibody responses elicited in horses against the glycoprotein D of EHV-1 (gD1), which is a protein involved in virus entry into cells.
- The gD1 protein shares 77% of its amino acid sequence similarity with the equivalent protein found in EHV-4 (gD4). As a result, it is common for both proteins to instigate the production of cross-reacting antibodies, including neutralizing antibodies that can inhibit a virus’s ability to infect cells.
- Despite an existing immunity against EHV-4, it does not offer protection against the more severe symptoms of EHV-1 infections like EHM.
The Research Methodology and Findings
- The researchers developed luciferase immunoprecipitation system (LIPS) assays, in which different sizes of the gD1 protein were used as antigens, to understand the antibody reactions against gD1 protein in horses.
- The LIPS assays were tested on blood serum samples from horses in Switzerland (60 samples) and Iceland (50 samples). Iceland is considered free of EHV-1.
- All the serum samples, barring one from Iceland, were found to have antibodies against both gD1 and gG4 (another protein in EHV-4), detected through the LIPS and ELISA methods respectively, indicating most horses were previously exposed to an infection with EHV-4.
- However, only 35% of Swiss samples and 14% of Icelandic samples had antibodies against gG1, implying a high percentage of antibodies against gD1 are likely due to cross-reaction resulting from EHV-4 infections.
- Interestingly, a smaller fragment of the gD1 protein (gD1_83) was found to be successful in recognizing type-specific antibodies against gD1, and these were mostly found in vaccinated horses.
Implications and Recommendations
- While the study does not conclusively establish that the presence of antibodies against specific areas (epitopes) of gD1 provides better protection, it suggests that future vaccine developments should focus on type-specific antigens.
- Researchers recommend avoiding type-common antigens that could lead to cross-reactivity and lack of specific immunity against EHV-1 or EHV-4 infections.
Cite This Article
APA
Schramm A, Ackermann M, Eichwald C, Aguilar C, Fraefel C, Lechmann J.
(2024).
Antibody reactions of horses against various domains of the EHV-1 receptor-binding protein gD1.
PLoS One, 19(7), e0301987.
https://doi.org/10.1371/journal.pone.0301987 Publication
Researcher Affiliations
- Institute of Virology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Institute of Virology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Institute of Virology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Institute of Virology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Institute of Virology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Institute of Virology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
MeSH Terms
- Animals
- Horses / immunology
- Herpesvirus 1, Equid / immunology
- Antibodies, Viral / immunology
- Antibodies, Viral / blood
- Viral Envelope Proteins / immunology
- Horse Diseases / virology
- Horse Diseases / immunology
- Horse Diseases / prevention & control
- Herpesvirus 4, Equid / immunology
- Herpesviridae Infections / veterinary
- Herpesviridae Infections / immunology
- Herpesviridae Infections / virology
- Cross Reactions / immunology
- Enzyme-Linked Immunosorbent Assay
- Antibodies, Neutralizing / immunology
- Antibodies, Neutralizing / blood
- Protein Domains / immunology
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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