Virulent and avirulent strains of equine arteritis virus induce different quantities of TNF-α and other proinflammatory cytokines in alveolar and blood-derived equine macrophages

Abstract

Equine arteritis virus (EAV) infects endothelial cells (ECs) and macrophages in horses, and many of the clinical manifestations of equine viral arteritis (EVA) reflect vascular injury. To further evaluate the potential role of EAV-induced, macrophage-derived cytokines in the pathogenesis of EVA, we infected cultured equine alveolar macrophages (AMφ), blood monocyte-derived macrophages (BMφ), and pulmonary artery ECs with either a virulent (KY84) or an avirulent (CA95) strain of EAV. EAV infection of equine AMφ, BMφ, and ECs resulted in their activation with increased transcription of genes encoding proinflammatory mediators, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α. Furthermore, the virulent KY84 strain of EAV induced significantly higher levels of mRNA encoding proinflammatory cytokines in infected AMφ and BMφ than did the avirulent CA95 strain. Treatment of equine ECs with the culture supernatants of EAV-infected AMφ and BMφ also resulted in EC activation with cell surface expression of E-selectin, whereas infection of ECs with purified EAV alone caused only minimal expression of E-selectin. The presence of TNF-α in the culture supernatants of EAV-infected equine AMφ, BMφ, and ECs was confirmed by bioassay, and the virulent KY84 strain of EAV induced significantly more TNF-α in all cell types than did the avirulent CA95 strain. Thus, the data indicate that EAV-induced, macrophage-derived cytokines may contribute to the pathogenesis of EVA in horses, and that the magnitude of the cytokine response of equine AMφ, BMφ, and ECs to EAV infection reflects the virulence of the infecting virus strain.