1. The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses
- Author
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Bettina Wagner, Susanna Babasyan, Gillian A. Perkins, Alicia Rollins, Alison E. Stout, Christine L. Wimer, Christiane L. Schnabel, Heather Freer, Amy L. Glaser, Nikolaus Osterrieder, and Laura B. Goodman
- Subjects
0301 basic medicine ,Male ,Cellular immunity ,Viral Diseases ,Pulmonology ,Physiology ,lcsh:Medicine ,Antibody Response ,Antibodies, Viral ,Biochemistry ,Body Temperature ,0403 veterinary science ,Random Allocation ,White Blood Cells ,Interferon ,Animal Cells ,Immune Physiology ,Medicine and Health Sciences ,lcsh:Science ,Immune Response ,Mammals ,ORF1 ,Immunity, Cellular ,Innate Immune System ,Multidisciplinary ,Immune System Proteins ,Virulence ,T Cells ,Eukaryota ,04 agricultural and veterinary sciences ,Herpesviridae Infections ,Isotype ,Virus Shedding ,Infectious Diseases ,Vertebrates ,Cytokines ,Female ,Antibody ,Cellular Types ,medicine.drug ,Herpesvirus 1, Equid ,Research Article ,040301 veterinary sciences ,Immune Cells ,Equines ,Immunology ,Viremia ,Biology ,Nose ,Virus ,Antibodies ,03 medical and health sciences ,Viral Proteins ,Immune system ,Immunity ,medicine ,Animals ,ORF71 ,Horses ,Secretion ,Blood Cells ,lcsh:R ,Organisms ,Biology and Life Sciences ,Proteins ,Cell Biology ,Molecular Development ,medicine.disease ,Virology ,neuropathogenic EHV-1 strain Ab4 ,030104 developmental biology ,Immunoglobulin G ,Immune System ,Mutation ,Amniotes ,Respiratory Infections ,biology.protein ,lcsh:Q ,Horse Diseases ,Physiological Processes ,Developmental Biology - Abstract
The equine herpesvirus type 1 (EHV-1) ORF1 and ORF71 genes have immune modulatory effects in vitro. Experimental infection of horses using virus mutants with multiple deletions including ORF1 and ORF71 showed promise as vaccine candidates against EHV-1. Here, the combined effects of ORF1 and ORF71 deletions from the neuropathogenic EHV-1 strain Ab4 on clinical disease and host immune response were further explored. Three groups of EHV-1 naive horses were experimentally infected with the ORF1/71 gene deletion mutant (Ab4ΔORF1/71), the parent Ab4 strain, or remained uninfected. In comparison to Ab4, horses infected with Ab4ΔORF1/71 did not show the initial high fever peak characteristic of EHV-1 infection. Ab4ΔORF1/71 infection had reduced nasal shedding (1/5 vs. 5/5) and, simultaneously, decreased intranasal interferon (IFN)-α, interleukin (IL)-10 and soluble CD14 secretion. However, Ab4 and Ab4ΔORF1/71 infection resulted in comparable viremia, suggesting these genes do not regulate the infection of the mononuclear cells and subsequent viremia. Intranasal and serum anti-EHV-1 antibodies to Ab4ΔORF1/71 developed slightly slower than those to Ab4. However, beyond day 12 post infection (d12pi) serum antibodies in both virus-infected groups were similar and remained increased until the end of the study (d114pi). EHV-1 immunoglobulin (Ig) G isotype responses were dominated by short-lasting IgG1 and long-lasting IgG4/7 antibodies. The IgG4/7 response closely resembled the total EHV-1 specific antibody response. Ex vivo re-stimulation of PBMC with Ab4 resulted in IFN-γ and IL-10 secretion by cells from both infected groups within two weeks pi. Flow cytometric analysis showed that IFN-γ producing EHV-1-specific T-cells were mainly CD8+/IFN-γ+ and detectable from d32pi on. Peripheral blood IFN-γ+ T-cell percentages were similar in both infected groups, albeit at low frequency (~0.1%). In summary, the Ab4ΔORF1/71 gene deletion mutant is less virulent but induced antibody responses and cellular immunity similar to the parent Ab4 strain.
- Published
- 2018