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

Equine herpesvirus-1 (EHV-1) infects equine endothelial cells (EECs) lining the small blood vessels in the central nervous system. However, the effect of type I IFN on EHV-1 replication in the EECs is not well studied. Thus, the primary objective of this study was to investigate the effect of type-I IFN on the replication of the neuropathogenic T953 strain of EHV-1 in vitro in EECs. The initial data showed that the EHV-1 was partly resistant to the biological effect of exogenously supplied recombinant equine IFN-α. Subsequent investigation into the mechanism of resistance showed that EHV-1 infection of EECs interfered with the STAT-1 phosphorylation through which type-I IFN exerts its antiviral effect. Immunofluorescence staining showed interference with the translocation of STAT-1 molecules from cytoplasm to nucleus confirming the virus mediated suppression of STAT-1 activation. Downstream of the JAK-STAT signaling, EHV-1 infection inhibited expression of cellular antiviral proteins including IFN-stimulated gene 56 (ISG56) and viperin. Taken together these findings suggest that the neuropathogenic T953 strain of EHV-1 evades the host innate immune response by inhibiting IFN and this may provide some insight into the pathogenesis of EHV-1 infection.