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

This research examined how the Equine Arteritis Virus (EAV) affects horses. It was found that virulent and avirulent strains of the virus induce differing levels of TNF-alpha and other proinflammatory cytokines in macrophages which may reflect on the virulence of the infecting virus strain.

Study Design and Approach

• The researchers set up a study to examine the effect of Equine Arteritis Virus (EAV) on horses.
• EAV infects the endothelial cells (ECs) and macrophages in horses. Endothelial cells line the interior surface of blood vessels and lymphatic vessels, while macrophages are a type of white blood cell that engulfs and digests cellular debris and pathogens.
• Many of the clinical manifestations or symptoms in horses affected by EAV such as fever, swelling, or inflammation of respiratory tract tissues or the blood vessels (a disease called Equine Viral Arteritis) are a reflection of vascular injury.
• To understand the potential role of EAV-induced, macrophage-derived cytokines in the pathogenesis or disease progression of EVA, the researchers infected cultured equine alveolar macrophages, blood monocyte-derived macrophages, and pulmonary artery ECs with either a virulent (KY84) or an avirulent (CA95) strain of EAV.

Key Findings

• The researchers found that EAV infection activated these cells and increased the transcription of genes encoding proinflammatory mediators, including Interleukin (IL)-1beta, IL-6, IL-8, and Tumor Necrosis Factor (TNF)-alpha. Proinflammatory mediators are substances released by various cell types in response to infection, injury, or immune events that amplify the inflammatory response.
• Interestingly, the more virulent KY84 strain of EAV induced significantly greater levels of mRNA encoding these proinflammatory cytokines in infected macrophages than the less dangerous CA95 strain.
• Treatment of equine ECs with the culture supernatants of EAV-infected macrophages also resulted in EC activation with cell surface expression of E-selectin, a complex protein molecule necessary for the immune response. In contrast, infection of ECs with purified EAV alone led to only minimal expression of E-selectin.
• The presence of TNF-alpha in the culture supernatants of EAV-infected macrophages and ECs was confirmed. The KY84 strain induced significantly more TNF-alpha in all cell types than the CA95 strain.

Conclusion

• From the study, the researchers concluded that EAV-induced, macrophage-derived cytokines may contribute to the pathogenesis of EVA in horses. The magnitude of the cytokine response of macrophages and ECs to EAV infection seems to reflect the virulence of the infecting virus strain.