Equine herpesvirus-1 infection disrupts interferon regulatory factor-3 (IRF-3) signaling pathways in equine endothelial cells
Equine herpesvirus-1 infection disrupts interferon regulatory factor-3 (IRF-3) signaling pathways in equine endothelial cells
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DOI：
10.1016/j.vetimm.2016.03.009
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发表时间：
2016-05-01
影响因子：
1.8
通讯作者：
Chambers, Thomas M.
中科院分区：
文献类型：
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作者：
Sarkar, Sanjay;Balasuriya, Udeni B. R.;Chambers, Thomas M.
马疱疹病毒-1 (EHV-1) 是马的主要呼吸道病毒病原体，可引起上呼吸道疾病、流产、新生儿死亡以及可能导致瘫痪和死亡的神经系统疾病。 EHV-1 最初在呼吸道上皮中复制，然后全身扩散到子宫和脊髓小血管内壁的内皮细胞，导致马流产和 EHM。与其他疱疹病毒一样，EHV-1 采用多种免疫逃避机制，包括抑制马内皮细胞 (EEC) 中 I 型干扰素 (IFN) 的产生。之前我们已经证明，EHV-1 的神经致病性 T953 菌株抑制 EEC 中 I 型 IFN 的产生，这是由病毒晚期基因产物介导的。但抑制机制尚不清楚。在这里，我们表明 EEC 的 T953 菌株感染诱导内源 IRF-3 蛋白的降解。这反过来又干扰了 IRF-3 信号通路的激活。 EHV-1感染引起NF-kappa B信号通路的激活，表明I型IFN产生的抑制可能是由于干扰IRF-3而不是NF-kappa B信号转导。 (C) 2016 Elsevier B.V. 保留所有权利。
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-kappa B signaling pathways, suggesting that inhibition of type-I IFN production is probably due to interference in IRF-3 and not NF-kappa B signal transduction. (C) 2016 Elsevier B.V. All rights reserved.