Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.
Abstract: Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EHV-1 (WT). Infection with either virus led to cytokine responses that coincided with the course of clinical disease, particularly the biphasic pyrexia, which correlates with respiratory disease and viremia, respectively. Similarly, both viruses caused suppression of proliferative T-cell responses on day 7 post infection (pi). The ΔORF1/ORF2 virus caused significantly shorter primary pyrexia and significantly reduced nasal shedding, and an attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared to WT-infected ponies. In conclusion, our findings are (i) that infection of ponies with EHV-1 leads to modulation of immune responses, which are correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of importance for disease outcome and modulation of cytokine responses.
Publication Date: 2011-02-07 PubMed ID: 21314906PubMed Central: PMC3045331DOI: 10.1186/1297-9716-42-23Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This research article explores the immune responses in ponies following an infection with a variant of Equine herpesvirus-1 (EHV-1) that has had its ORF1 and ORF2 genes removed. The results indicate that these deleted genes significantly affect disease outcome and the response of the immune system.
Investigation into EHV-1
- The researchers approached the persistent problem of EHV-1 in ponies by studying the immune responses following an infection with a modified variant of the virus. This variant had its suspected immunoregulatory genes, ORF1 and ORF2, removed.
- With the widespread use of vaccines, EHV-1 continues to persist as a significant issue. The hypothesis is that the virus possesses immunomodulatory properties that prevent a protective immune response either from the vaccine or from prior infection. The ORF1 and ORF2 genes have been identified as possible candidates with these immune-regulating properties.
Understanding immune responses to EHV-1
- An infection study with ponies was conducted to lay out the exact immune responses following an EHV-1 infection and to see if the ORF1/2-deleted variant had different impacts on disease progression and immune regulation compared to the wild version of the virus.
- With either virus, cytokine responses occurred alongside the clinical disease course, specifically the biphasic pyrexia—a fever that correlates with respiratory disease and viremia. Both the ORF1/2-deleted virus and its wild-type counterpart also suppressed the proliferation of T-cells on the 7th day after infection.
Importance of ORF1/2 in disease outcomes and immune response
- The ORF1/2-deleted variant of the virus caused a significantly shorter primary fever and less nasal shedding than the wild type. This variant also experienced a decreased decrease in IL-8 in peripheral blood mononuclear cells (PBMCs) and increased Tbet responses compared to those ponies infected with the wild type.
- The results suggest that the ORF1/2 genes hold substantial importance in disease outcomes and in modulating cytokine responses. Ultimately, the study concludes that infection of ponies with EHV-1 leads to immune response modulation, correlates with disease pathogenesis, and shows the regulatory importance of ORF1/2 genes.
Cite This Article
APA
Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP.
(2011).
Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.
Vet Res, 42(1), 23.
https://doi.org/10.1186/1297-9716-42-23 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W, Drake Rd, Fort Collins, Colorado 80523, USA. husseygs@colostate.edu.
MeSH Terms
- Adaptive Immunity
- Animals
- Antibodies, Viral / blood
- Cytokines / blood
- Cytokines / genetics
- Enzyme-Linked Immunosorbent Assay / veterinary
- Female
- Herpesviridae Infections / immunology
- Herpesviridae Infections / veterinary
- Herpesviridae Infections / virology
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / immunology
- Herpesvirus 1, Equid / metabolism
- Horse Diseases / immunology
- Horse Diseases / virology
- Horses
- Immunity, Innate
- Male
- Nasal Mucosa / virology
- RNA, Messenger / analysis
- Random Allocation
- Viral Proteins / genetics
- Viral Proteins / metabolism
- Viremia / immunology
- Viremia / veterinary
- Viremia / virology
- Virus Shedding
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Citations
This article has been cited 19 times.- Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G. A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1.. Front Vet Sci 2021;8:674850.
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