title: 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.
authors.affiliation: 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.
authors.forename: Gisela
authors.initials: G
authors.lastname: Soboll Hussey
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hussey
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.forename: David W
authors.initials: DW
authors.lastname: Horohov
authors.forename: Gerlinde R
authors.initials: GR
authors.lastname: Van de Walle
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Osterrieder
authors.forename: Lutz S
authors.initials: LS
authors.lastname: Goehring
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Rao
authors.forename: David P
authors.initials: DP
authors.lastname: Lunn
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D004861:Herpesvirus 1, Equid / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006734:Horse Diseases / Q000276:immunology* / Q000821:virology; D006736:Horses; D007113:Immunity, Innate; D008297:Male; D009297:Nasal Mucosa / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014766:Viremia / Q000276:immunology / Q000662:veterinary / Q000821:virology; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D012333:RNA, Messenger; D014764:Viral Proteins