title: Equine herpesvirus-1 infection disrupts interferon regulatory factor-3 (IRF-3) signaling pathways in equine endothelial cells.
abstract: Equine herpesvirus-1 (EHV-1) is a major respiratory viral pathogen of horses, causing upper respiratory tract disease, abortion, neonatal death, and neurological disease that may lead to paralysis and death. EHV-1 replicates initially in the respiratory epithelium and then spreads systemically to endothelial cells lining the small blood vessels in the uterus and spinal cord leading to abortion and EHM in horses. Like other herpesviruses, EHV-1 employs a variety of mechanisms for immune evasion including suppression of type-I interferon (IFN) production in equine endothelial cells (EECs). Previously we have shown that the neuropathogenic T953 strain of EHV-1 inhibits type-I IFN production in EECs and this is mediated by a viral late gene product. But the mechanism of inhibition was not known. Here we show that T953 strain infection of EECs induced degradation of endogenous IRF-3 protein. This in turn interfered with the activation of IRF-3 signaling pathways. EHV-1 infection caused the activation of the NF-κB signaling pathways, suggesting that inhibition of type-I IFN production is probably due to interference in IRF-3 and not NF-κB signal transduction.
authors.affiliation: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, USA. Electronic address: sanjaysarkarvet@gmail.com.
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.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Chambers
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006566:Herpesviridae Infections / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D004861:Herpesvirus 1, Equid; D006734:Horse Diseases / Q000378:metabolism / Q000821:virology*; D006736:Horses; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D007370:Interferon Type I / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D016328:NF-kappa B
keywords: EHV-1; Equine herpesvirus-1; IFN-β; IRF-3; Immune evasion; Innate immunity