TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus
TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus
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DOI：
10.1099/vir.0.006288-0
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发表时间：
2009-03-01
影响因子：
3.8
通讯作者：
Mechti, Nadir
中科院分区：
文献类型：
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作者：
Eldin, Patrick;Papon, Laura;Mechti, Nadir
干扰素（IFN）系统是先天免疫的主要效应器，它为随后针对多种病原体建立适应性免疫反应提供了时间。它们的多种生物作用被认为是由靶细胞中诱导的特定但通常重叠的细胞基因的产物介导的。泛素连接酶的成员的三部基元（TRIM）蛋白家族已经出现ifn包括蛋白参与先天和适应性免疫。在本报告中，我们提供证据表明TRIM22是一种功能性的E3泛素连接酶，它本身也泛素化。我们证明TRIM22的表达导致HeLa细胞对脑心肌炎病毒感染的病毒保护。这种作用取决于其E3泛素化活性，因为在表达泛素化活性缺陷的trim22缺失突变体的细胞中没有观察到抗病毒作用。与此一致，TRIM22与病毒3C蛋白酶（3C(PRO)）相互作用并介导其泛素化。总之，我们的研究结果表明TRIM22 E3泛素连接酶活性代表了IFN诱导的针对小核糖核酸病毒的新抗病毒途径。
The interferon (IFN) system is a major effector of the innate immunity that allows time for the subsequent establishment of an adaptive immune response against a wide-range of pathogens. Their diverse biological actions are thought to be mediated by the products of specific but usually overlapping sets of cellular genes induced in the target cells. Ubiquitin ligase members of the tripartite motif (TRIM) protein family have emerged as IFN-incluced proteins involved in both innate and adaptive immunity. In this report, we provide evidence that TRIM22 is a functional E3 ubiquitin ligase that is also ubiquitinated itself. We demonstrate that TRIM22 expression leads to a viral protection of HeLa cells against encephalomyocarditis virus infections. This effect is dependent upon its E3 ubiquitinating activity, since no antiviral effect was observed in cells expressing a TRIM22-deletion mutant defective in ubiquitinating activity. Consistent with this, TRIM22 interacts with the viral 3C protease (3C(PRO)) and mediates its ubiquitination. Altogether, our findings demonstrate that TRIM22 E3 ubiquitin ligase activity represents a new antiviral pathway induced by IFN against picornaviruses.