title: The neuropathogenic T953 strain of equine herpesvirus-1 inhibits type-I IFN mediated antiviral activity in equine endothelial cells.
abstract: 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.
authors.affiliation: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, USA.
authors.forename: Udeni B R
authors.initials: UB
authors.lastname: Balasuriya
authors.affiliation: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Horohov
authors.affiliation: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, USA. Electronic address: tmcham1@uky.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Chambers
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects; D006566:Herpesviridae Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D004861:Herpesvirus 1, Equid / Q000187:drug effects* / Q000276:immunology; D006734:Horse Diseases / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D006736:Horses; D007370:Interferon Type I / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D050794:STAT1 Transcription Factor
keywords: Equine herpesvirus-1; Interferon-α; STAT-1