Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity
Abstract Background Equine herpesvirus type 1 (EHV-1) induces respiratory infection, abortion, and neurologic disease with significant impact. Virulence factors contributing to infection and immune evasion are of particular interest. A potential virulence factor of the neuropathogenic EHV-1 strain A...
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BMC
2018-08-01
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| Series: | BMC Veterinary Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12917-018-1563-4 |
| _version_ | 1818668390404849664 |
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| author | Christiane L. Schnabel Christine L. Wimer Gillian Perkins Susanna Babasyan Heather Freer Christina Watts Alicia Rollins Nikolaus Osterrieder Bettina Wagner |
| author_facet | Christiane L. Schnabel Christine L. Wimer Gillian Perkins Susanna Babasyan Heather Freer Christina Watts Alicia Rollins Nikolaus Osterrieder Bettina Wagner |
| author_sort | Christiane L. Schnabel |
| collection | DOAJ |
| description | Abstract Background Equine herpesvirus type 1 (EHV-1) induces respiratory infection, abortion, and neurologic disease with significant impact. Virulence factors contributing to infection and immune evasion are of particular interest. A potential virulence factor of the neuropathogenic EHV-1 strain Ab4 is ORF2. This study on 24 Icelandic horses, 2 to 4 years of age, describes the infection with EHV-1 Ab4, or its deletion mutant devoid of ORF2 (Ab4ΔORF2) compared to non-infected controls (each group n = 8). The horses’ clinical presentation, virus shedding, viremia, antibody and cellular immune responses were monitored over 260 days after experimental infection. Results Infection with Ab4ΔORF2 reduced fever and minimized nasal virus shedding after infection compared to the parent virus strain Ab4, while Ab4ΔORF2 established viremia similar to Ab4. Concurrently with virus shedding, intranasal cytokine and interferon α (IFN-α) production increased in the Ab4 group, while horses infected with Ab4ΔORF2 expressed less IFN-α. The antibody response to EHV-1 was evaluated by a bead-based multiplex assay and was similar in both infected groups, Ab4 and Ab4ΔORF2. EHV-1 specific immunoglobulin (Ig) G1 was induced 8 days after infection (d8 pi) with a peak on d10–12 pi. EHV-1 specific IgG4/7 increased starting on d10 pi, and remained elevated in serum until the end of the study. The intranasal antibody response to EHV-1 was dominated by the same IgG isotypes and remained elevated in both infected groups until d130 pi. In contrast to the distinct antibody response, no induction of EHV-1 specific T-cells was detectable by flow cytometry after ex vivo re-stimulation of peripheral blood mononuclear cells (PBMC) with EHV-1 in any group. The cellular immune response was characterized by increased secretion of IFN-γ and interleukin10 in response to ex vivo re-stimulation of PBMC with EHV-1. This response was present during the time of viremia (d5–10 pi) and was similar in both infected groups, Ab4 and Ab4ΔORF2. Conclusions ORF2 is a virulence factor of EHV-1 Ab4 with impact on pyrexia and virus shedding from the nasal mucosa. In contrast, ORF2 does not influence viremia. The immunogenicity of the Ab4ΔORF2 and parent Ab4 viruses are identical. Graphical abstract Graphical abstract – Deletion of ORF2 reduces virulence of EHV-1 Ab4. Graphical summary of the main findings of this study: ORF2 is a virulence factor of EHV-1 Ab4 with impact on pyrexia and virus shedding from the nasal mucosa. |
| first_indexed | 2024-12-17T06:35:33Z |
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| last_indexed | 2024-12-17T06:35:33Z |
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| spelling | doaj.art-600b826a016745088682bf76f8c4932e2022-12-21T22:00:01ZengBMCBMC Veterinary Research1746-61482018-08-0114111510.1186/s12917-018-1563-4Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicityChristiane L. Schnabel0Christine L. Wimer1Gillian Perkins2Susanna Babasyan3Heather Freer4Christina Watts5Alicia Rollins6Nikolaus Osterrieder7Bettina Wagner8Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell UniversityInstitut für Virologie, Freie Universität BerlinDepartment of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell UniversityAbstract Background Equine herpesvirus type 1 (EHV-1) induces respiratory infection, abortion, and neurologic disease with significant impact. Virulence factors contributing to infection and immune evasion are of particular interest. A potential virulence factor of the neuropathogenic EHV-1 strain Ab4 is ORF2. This study on 24 Icelandic horses, 2 to 4 years of age, describes the infection with EHV-1 Ab4, or its deletion mutant devoid of ORF2 (Ab4ΔORF2) compared to non-infected controls (each group n = 8). The horses’ clinical presentation, virus shedding, viremia, antibody and cellular immune responses were monitored over 260 days after experimental infection. Results Infection with Ab4ΔORF2 reduced fever and minimized nasal virus shedding after infection compared to the parent virus strain Ab4, while Ab4ΔORF2 established viremia similar to Ab4. Concurrently with virus shedding, intranasal cytokine and interferon α (IFN-α) production increased in the Ab4 group, while horses infected with Ab4ΔORF2 expressed less IFN-α. The antibody response to EHV-1 was evaluated by a bead-based multiplex assay and was similar in both infected groups, Ab4 and Ab4ΔORF2. EHV-1 specific immunoglobulin (Ig) G1 was induced 8 days after infection (d8 pi) with a peak on d10–12 pi. EHV-1 specific IgG4/7 increased starting on d10 pi, and remained elevated in serum until the end of the study. The intranasal antibody response to EHV-1 was dominated by the same IgG isotypes and remained elevated in both infected groups until d130 pi. In contrast to the distinct antibody response, no induction of EHV-1 specific T-cells was detectable by flow cytometry after ex vivo re-stimulation of peripheral blood mononuclear cells (PBMC) with EHV-1 in any group. The cellular immune response was characterized by increased secretion of IFN-γ and interleukin10 in response to ex vivo re-stimulation of PBMC with EHV-1. This response was present during the time of viremia (d5–10 pi) and was similar in both infected groups, Ab4 and Ab4ΔORF2. Conclusions ORF2 is a virulence factor of EHV-1 Ab4 with impact on pyrexia and virus shedding from the nasal mucosa. In contrast, ORF2 does not influence viremia. The immunogenicity of the Ab4ΔORF2 and parent Ab4 viruses are identical. Graphical abstract Graphical abstract – Deletion of ORF2 reduces virulence of EHV-1 Ab4. Graphical summary of the main findings of this study: ORF2 is a virulence factor of EHV-1 Ab4 with impact on pyrexia and virus shedding from the nasal mucosa.http://link.springer.com/article/10.1186/s12917-018-1563-4HorseEHV-1ORF2Virulence factorImmunoglobulinMucosal immune response |
| spellingShingle | Christiane L. Schnabel Christine L. Wimer Gillian Perkins Susanna Babasyan Heather Freer Christina Watts Alicia Rollins Nikolaus Osterrieder Bettina Wagner Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity BMC Veterinary Research Horse EHV-1 ORF2 Virulence factor Immunoglobulin Mucosal immune response |
| title | Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity |
| title_full | Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity |
| title_fullStr | Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity |
| title_full_unstemmed | Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity |
| title_short | Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity |
| title_sort | deletion of the orf2 gene of the neuropathogenic equine herpesvirus type 1 strain ab4 reduces virulence while maintaining strong immunogenicity |
| topic | Horse EHV-1 ORF2 Virulence factor Immunoglobulin Mucosal immune response |
| url | http://link.springer.com/article/10.1186/s12917-018-1563-4 |
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