Equine herpesvirus-1 infection disrupts interferon regulatory factor-3 (IRF-3) signaling pathways in equine endothelial cells.

This research article explores the mechanism by which the equine herpesvirus-1 (EHV-1), a common horse respiratory virus, disrupts the immune system of its host by manipulating its signaling pathways, specifically the Interferon Regulatory Factor-3 (IRF-3) pathway, in equine endothelial cells (EECs).

Background

• The paper discusses how EHV-1 is a serious issue in the equine population, leading to upper respiratory tract disease, abortion, neonatal death, and neurological disease that can result in paralysis and death in horses.
• EHV-1 begins replication in the respiratory epithelium, and from there, it manages to spread across the animal’s body and infiltrate endothelial cells. These cells line the small blood vessels in key locations like the uterus and spinal cord, which connects to the manifestation of severe symptoms.

Immune Evasion and Previous Findings

• EHV-1, like many other herpesviruses, has found a method to evade the immune system. The virus suppresses the production of type-I interferon (IFN) in equine endothelial cells, an important part of the immune response against viral infections.
• Previous research from the same team has led to the discovery that a strain of EHV-1, “T953”, was inhibiting type-I IFN production in EECs, effectively lowering the host’s immune response. This action was found to be orchestrated by a viral late gene product, but the exact procedure of inhibition wasn’t identified.

New Discoveries

• Through this study, the researchers found that upon infection of EECs with the T953 strain, the virus results in degradation of the existing IRF-3 protein which interferes with the action of the IRF-3 signaling pathway. It is important to highlight that IRF-3 plays a critical role in the activation of IFN genes during a viral attack.
• Additionally, researchers found that EHV-1 infection triggers the activation of the NF-κB signaling pathways. This lead to the suggestion that the inhibition of type-I IFN production was primarily rooted in disruption of the IRF-3 pathway, and not the NF-κB signal transduction, thus isolating the primary area of effect.