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.

Neonatal Immunization with a Single IL-4/Antigen Dose Induces Increased Antibody Responses after Challenge Infection with Equine Herpesvirus Type 1 (EHV-1) at Weanling Age

“…All weanlings developed a fever, mild respiratory clinical signs, nasal EHV-1 shedding and viremia. All of these parameters observed in weanlings from EHV-1 naïve mares were similar to those described in previous EHV-1 infection studies in older horses [45–47]. Neurological signs were not expected after infection with the non-neurogenic NY03 strain and were not observed.…”

Major Histocompatibility Complex Class I Downregulation Induced by Equine Herpesvirus Type 1 pUL56 Is through Dynamin-Dependent Endocytosis

“…In dendritic cells, for example, intracellular transport of CD63 is associated with antigen presentation by MHC-II (70). The implication of pUL56 in downregulating CD46 and CD63 may suggest that it functions as a more promiscuous immune modulator, a notion that is supported by the results obtained in equids infected with the Ab4 mutant unable to express the protein (71).…”

Plasma D‐Dimer Concentrations during ExperimentalEHV‐1 Infection of Horses

“…A mainly proinflammatory cytokinemia could also provide a good explanation of the viremia‐associated fevers during EHV‐1 infections. Few studies, in vitro or in vivo , have focused on cytokine and chemokine production during EHV‐1 infection mainly using PBMC . However, none of the cytokines/chemokines identified in these studies could be linked to DD production as it occurs in other species; neither was there significant overlap with viremia.…”