Accumulation of the proinflammatory cytokine endothelial-monocyte-activating polypeptide II in ramified microglial cells in brains of Borna virus infected Lewis rats

Borna disease virus (BDV) infection of adult Lewis rats induces a severe and often fatal neurologic disease characterized by a massive mononuclear meningo-encephalitis, and activation of microglial cells. Therefore, we analyzed expression of endothelial monocyte activating polypeptide II (EMAP II) by immunohistology as a marker for activation of microglial cells in BDV infected rat brains. EMAP II is a chemotactic peptide, inducing activation of macrophages and endothelial cells, and is considered a proinflammatory mediator of the innate immune system. An up to 30-fold increase in numbers of EMAP II+ microglial cells and a massive expression by infiltrating macrophages at perivascular inflammatory foci was observed in infected brains, with a maximum on day 25 after infection. These results provide evidence that EMAP II contributes to immune responses in inflammatory processes caused by viral infections.