Ubiquitination and proteasomal degradation of interferon regulatory factor-3 induced by Npro from a cytopathic bovine viral diarrhea virus
Ubiquitination and proteasomal degradation of interferon regulatory factor-3 induced by Npro from a cytopathic bovine viral diarrhea virus
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DOI：
10.1016/j.virol.2007.04.023
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发表时间：
2007-09-30
期刊：
影响因子：
3.7
通讯作者：
Li, Kui
中科院分区：
文献类型：
--
作者：
Chen, Zihong;Rijnbrand, Rene;Li, Kui
牛病毒性腹泻病毒（BVDV）感染的发病机制是复杂的，只有部分了解。感染细胞病变（cp）BVDV（在体内不持续存在）的细胞中是否产生干扰素仍然存在争议。我们在这里表明，cpBVDV（NADL株）不诱导细胞培养物中的干扰素反应，并阻止干扰素刺激基因的诱导超感染副粘病毒。cpBVDV感染导致干扰素调节因子3（IRF-3）（一种控制干扰素合成的细胞转录因子）显著缺失。这归因于Npro的表达，而不是其蛋白酶活性。Npro与IRF-3相互作用，在其被病毒诱导的磷酸化激活之前，导致IRF-3的多聚泛素化和随后的蛋白酶体降解。El泛素活化酶的热失活防止Npro诱导的IRF-3损失。这些数据表明，抑制干扰素的产生是ncp和cpBVDV的共同特征，并提供了关于IRF-3调节瘟病毒发病机制的新见解。爱思唯尔公司出版
The pathogenesis of bovine viral diarrhea virus (BVDV) infections is complex and only partly understood. It remains controversial whether interferon is produced in cells infected with cytopathic(cp) BVDVs which do not persist in vivo. We show here that a cpBVDV (NADL strain) does not induce interferon responses in cell culture and blocks induction of interferon-stimulated genes by a super-infecting paramyxovirus. cpBVDV infection causes a marked loss of interferon regulatory factor 3 (IRF-3), a cellular transcription factor that controls interferon synthesis. This is attributed to expression of Npro, but not its protease activity. Npro interacts with IRF-3, prior to its activation by virus-induced phosphorylation, resulting in polyubiquitination and subsequent proteasomal degradation of IRF-3. Thermal inactivation of the El ubiquitin-activating enzyme prevents Npro-induced IRF-3 loss. These data suggest that inhibition of interferon production is a shared feature of both ncp and cpBVDVs and provide new insights regarding IRF-3 regulation in pestivirus pathogenesis. Published by Elsevier Inc.