Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1
Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1
复制标题
DOI：
10.1099/vir.0.81074-0
复制
发表时间：
2005-08-01
影响因子：
3.8
通讯作者：
Mechti, N
中科院分区：
文献类型：
--
作者：
Espert, L;Degols, G;Mechti, N
干扰素（IFN）编码一个分泌蛋白家族，其提供对抗病毒感染的前线防御。ISG 20是DEDD核酸外切酶超家族的一个新的3' -> 5'核糖核酸外切酶成员，它代表了IFN作用机制中的一种新的抗病毒途径。在这份报告中，它表明，ISG 20的表达是快速和强烈诱导人类免疫缺陷病毒1型（HIV-1）感染。此外，证实了表达ISG 20蛋白的HIV-1衍生病毒（HIV-1（NL 4 - 3 ISG 20））的复制动力学在CEM细胞和外周血单核细胞中均被延迟。在过表达核酸外切酶活性缺陷的突变ISG 20蛋白的细胞中未观察到抗病毒作用，表明抗病毒作用是由于ISG 20的核酸外切酶活性。奇怪的是，尽管ISG 20蛋白具有抗病毒活性，但在HIV-1（NL 4 - 31 SG 20）感染的细胞中观察到的病毒拯救不是由于ISG 20转基因的突变或部分缺失，这表明病毒能够抵消细胞防御。此外，在HIV-1（NL 4 - 31 SG 20）感染的细胞中，HIV-1诱导的细胞凋亡显著减少，表明HIV-1（NL 4）-（31 SG 20）的出现与HIV-1诱导的细胞凋亡的抑制有关。总之，这些数据反映了病毒在过表达ISG 20的细胞中复制的无效性，并证明ISG 20代表了IFN介导的抗HIV-1抗病毒屏障中的新因子。
Interferons (IFNs) encode a family of secreted proteins that provide the front-line defence against viral infections. It was recently shown that ISG20, a new 3' -> 5' exoribonuclease member of the DEDD superfamily of exonucleases, represents a novel antiviral pathway in the mechanism of IFN action. In this report, it was shown that ISG20 expression is rapidly and strongly induced during human immunodeficiency virus type 1 (HIV-1) infection. In addition, it was demonstrated that the replication kinetics of an HIV-1-derived virus expressing the ISG20 protein (HIV-1(NL4-3lSG20)) was delayed in both CEM cells and peripheral blood mononuclear cells. No antiviral effect was observed in cells overexpressing a mutated ISG20 protein defective in exonuclease activity, suggesting that the antiviral effect was due to the exonuclease activity of ISG20. Paradoxically, despite the antiviral activity of ISG20 protein, virus rescue observed in HIV-1(NL4-3lSG20)-infected cells was not due to mutation or partial deletion of the ISG20 transgene, suggesting that the virus was able to counteract the cellular defences. In addition, HIV-1-induced apoptosis was significantly reduced in HIV-1(NL4-3lSG20)-infected cells suggesting that emergence of HIV-1(NL4)-(3lSG20) was associated with the inhibition of HIV-1-induced apoptosis. Altogether, these data reflect the ineffectiveness of virus replication in cells overexpressing ISG20 and demonstrate that ISG20 represents a new factor in the IFN-mediated antiviral barrier against HIV-1.