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