Principal Investigator: Tracy Stokol

DESCRIPTION (provided by applicant): 

Equine herpes virus type 1 (EHV-1) infection causes significant morbidity and mortality in horses as a consequence of outbreaks of respiratory disease, abortion and neurologic disease. Outbreaks are associated with newly introduced actively infected animals or recrudescence of viral shedding by latently infected horses following stress. This disease remains a major problem for horse owners, as available vaccines do not prevent clinical disease or establishment of latency. The innate immune response guides subsequent adaptive immunity to virus infection and has been shown to be a major determinant of pathogenic outcome for other viruses. EHV-1 infects monocytes, which are critical immune cells in the innate response to viral infection. A major gap in our understanding of EHV-1 pathogenesis is how the innate immune response is modulated by viral infection. A further complication is that, in other species such as pigs, ruminants and humans, two major monocyte subsets can be defined based on surface molecule expression and chemokine profiles: M1 or pro-inflammatory monocytes and M2 or anti-inflammatory monocytes. Viruses are known to manipulate these monocyte subsets to subvert or suppress immunity, promote replication and dissemination, and establish latency. The M1 and M2 monocyte subsets have not been properly defined in horses. Moreover, it is unknown if these monocyte subsets have different susceptibilities to EHV-1 infection, as reported for other viruses. We have found that there is a dominant monocyte subset in equine blood that expresses CD163, a scavenger receptor involved in resolution of inflammation. This data indicates that these cells are akin to M2 or anti-inflammatory monocytes, with a less numerous subset of CD163-negative cells likely representing M1 or pro-inflammatory monocytes. Our global hypothesis is that these monocyte subsets will respond differently to EHV-1 infection and that this differential innate response will then influence adaptive immunity to EHV-1 and viral pathogenicity. Before we can begin to test this hypothesis, it is important to first determine if these monocyte subsets can be infected to similar extents by EHV-1, which is the goal of this pilot proposal.