The golden Syrian hamster (Mesocricetus auratus) as a model to decipher relevant pathogenic aspects of sheep-associated malignant catarrhal fever

Malignant catarrhal fever (MCF) is an often fatal, sporadic gammaherpesvirus-induced disease of ruminants with global relevance. Ovine gammaherpesvirus-2 (OvHV-2), with sheep as its reservoir host, is a major cause of MCF in susceptible species. Despite extensive research on the molecular aspects of the disease, its pathogenesis is not yet fully understood. The present study re-established the Syrian golden hamster (Mesocricetus auratus) as an amenable animal model of MCF and applied complementary in situ approaches to confirm recent findings in natural disease that could shed new light on pathogenic aspects of MCF. These showed that systemic OvHV-2 infection is associated with T-cell and macrophage-dominated mononuclear infiltrates and vasculitis in various organs. Both T-cells and monocytes/macrophages harbor the virus, and infected leukocytes are abundant in the infiltrates. The results also indicate that OvHV-2 has a broader target cell spectrum, including vascular endothelial cells and selected squamous epithelia. The former supports the interpretation that the inflammatory processes develop due to circulating, activated, infected T-cells and monocytes that home to tissues and emigrate from vessels prone to leukocyte emigration, possibly with direct interaction between virus-infected leukocytes and endothelial cells. The latter supports the hypothesis of graft versus host disease scenario, without viral cytopathic effect on epithelial cells but infiltration of the mucosa by infected T-cells and macrophages. The disease processes are accompanied by evidence of expansion of the T-cell compartments and the monocyte/macrophage pool in lymphatic tissues and bone marrow.