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

Sanjay Sarkar; Udeni B.R. Balasuriya; David W. Horohov; Thomas M. Chambers

doi:10.1016/j.vetimm.2016.03.009

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

Sanjay Sarkar, Udeni B.R. Balasuriya, David W. Horohov, Thomas M. Chambers

Veterinary Science

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English
Pages (from-to)	1-9
Number of pages	9
Journal	Veterinary Immunology and Immunopathology
Volume	173
DOIs	https://doi.org/10.1016/j.vetimm.2016.03.009
State	Published - May 1 2016

Bibliographical note

Funding Information:
We wish to acknowledge the generous technical assistance of Ms. Stephanie Reedy. We thank Dr. Adolfo Garcia-Sastre (Mount Sinai School of Medicine, New York), Dr. Dennis O’Callaghan (Louisiana State University) for provision of reagents and Dr. Klaus Osterrieder (Institut für Virologie) for his helpful discussion. This work was supported by grants from the American Quarter Horse Foundation and the Grayson Jockey Club Research Foundation . Sanjay Sarkar was supported by a fellowship from the Geoffrey C. Hughes Foundation . The work is part of a project of the Kentucky Agricultural Experiment Station (KY014041 and KY041042) and is published with the approval of the Director (publication no. 16-14-028).

Publisher Copyright:
© 2016 Elsevier B.V.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

EHV-1
Equine herpesvirus-1
IFN-β
IRF-3
Immune evasion
Innate immunity

ASJC Scopus subject areas

Immunology
Veterinary (all)

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10.1016/j.vetimm.2016.03.009

Cite this

@article{36535b5f2aa94845afb675c87db5253d,

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.",

keywords = "EHV-1, Equine herpesvirus-1, IFN-β, IRF-3, Immune evasion, Innate immunity",

author = "Sanjay Sarkar and Balasuriya, {Udeni B.R.} and Horohov, {David W.} and Chambers, {Thomas M.}",

note = "Funding Information: We wish to acknowledge the generous technical assistance of Ms. Stephanie Reedy. We thank Dr. Adolfo Garcia-Sastre (Mount Sinai School of Medicine, New York), Dr. Dennis O{\textquoteright}Callaghan (Louisiana State University) for provision of reagents and Dr. Klaus Osterrieder (Institut f{\"u}r Virologie) for his helpful discussion. This work was supported by grants from the American Quarter Horse Foundation and the Grayson Jockey Club Research Foundation . Sanjay Sarkar was supported by a fellowship from the Geoffrey C. Hughes Foundation . The work is part of a project of the Kentucky Agricultural Experiment Station (KY014041 and KY041042) and is published with the approval of the Director (publication no. 16-14-028). Publisher Copyright: {\textcopyright} 2016 Elsevier B.V. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.vetimm.2016.03.009",

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AU - Horohov, David W.

AU - Chambers, Thomas M.

N1 - Funding Information: We wish to acknowledge the generous technical assistance of Ms. Stephanie Reedy. We thank Dr. Adolfo Garcia-Sastre (Mount Sinai School of Medicine, New York), Dr. Dennis O’Callaghan (Louisiana State University) for provision of reagents and Dr. Klaus Osterrieder (Institut für Virologie) for his helpful discussion. This work was supported by grants from the American Quarter Horse Foundation and the Grayson Jockey Club Research Foundation . Sanjay Sarkar was supported by a fellowship from the Geoffrey C. Hughes Foundation . The work is part of a project of the Kentucky Agricultural Experiment Station (KY014041 and KY041042) and is published with the approval of the Director (publication no. 16-14-028). Publisher Copyright: © 2016 Elsevier B.V. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.

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N2 - 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.

AB - 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.

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JO - Veterinary Immunology and Immunopathology

JF - Veterinary Immunology and Immunopathology

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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