The neuropathogenic T953 strain of equine herpesvirus-1 inhibits type-I IFN mediated antiviral activity in equine endothelial cells.

This research article investigates how the neuropathogenic T953 strain of equine herpesvirus-1 (EHV-1), a virus that affects horses, can resist the immune response of the host by inhibiting the effect of type-I interferon (IFN). The research discovered that the strain interferes with antiviral processes in the body of the horse, supporting its survival and propagation.

Method and Initial Findings

• The researchers began by infecting equine endothelial cells (EECs), which line the small blood vessels in horses’ central nervous system, with the neuropathic strain and supplying the same with recombinant equine interferon-alpha (IFN-α) externally. The initial data showed that the virus remained partly resistant to the effect of IFN-α, thus indicating a mechanism by which the virus counters the host’s immune response.

Investigating the Mechanism of Resistance

• The team went on to investigate this resistance mechanism, focusing on how Echovirus-1 interferes with one of the main avenues through which type-I IFN exerts its antiviral activities – the process of STAT-1 phosphorylation.
• By employing immunofluorescence staining, the researchers demonstrated that EHV-1 disrupts the translocation of STAT-1 molecules from the cytoplasm to the nucleus, confirming that the virus suppresses the activation of STAT-1, which is a key part of the IFN response.

The Role of the JAK-STAT Signaling Pathway

• EHV-1 also appears to inhibit the downstream effects of the JAK-STAT signaling pathway, a fundamental step in the IFN response.
• Specifically, the researchers showed that the virus impedes the expression of cellular antiviral proteins such as IFN-stimulated gene 56 (ISG56) and viperin. These findings suggest that the virus effectively evades the host animal’s innate immune response.

Conclusion

• The results of this study suggest that the T953 strain of EHV-1 can circumvent the immune response of a horse through selective impairment of the host’s interferon pathway.
• This understanding adds to our knowledge of EHV-1 pathogenesis and may guide more effective strategies for treatment and prevention of this equine disease.