Molecular Mechanisms for the Adaptive Switching Between the OAS/RNase L and OASL/RIG-I Pathways in Birds and Mammals.
Molecular Mechanisms for the Adaptive Switching Between the OAS/RNase L and OASL/RIG-I Pathways in Birds and Mammals.
复制标题
鸟类和哺乳动物中 OAS/RNase L 和 OASL/RIG-I 通路自适应切换的分子机制
DOI：
10.3389/fimmu.2018.01398
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Rong E;Wang X;Chen H;Yang C;Hu J;Liu W;Wang Z;Chen X;Zheng H;Pu J;Sun H;Smith J;Burt DW;Liu J;Li N;Huang Y
宿主细胞产生OAS/RNase L [2′-5′-寡腺苷酸合成酶（OAS）/核糖核酸酶L]系统以降解细胞和病毒RNA，和/或OASL/RIG-I（2′-5′-OAS样/视黄酸诱导蛋白I）系统以增强RIG-I介导的IFN诱导，从而提供抗病毒感染的第一道防线。2′-5′-OAS-like（OASL）蛋白可能通过其典型的OAS样结构域（OLD）激活OAS/RNase L系统，或通过其两个串联的泛素样结构域（UBLs）模拟K63连接的pUb增强OASL/RIG-I系统的抗病毒活性。我们首先描述了不同禽类（鸭和鸵鸟）OASL通过以UBL依赖性方式激活和放大OAS/RNase L途径来抑制广泛的RNA病毒复制。这与哺乳动物酶促OASL形成鲜明对比，后者以不依赖UBL的方式激活和放大OAS/RNase L途径，类似于2 '-5'-寡腺苷酸合成酶1（OAS 1）。我们进一步发现，鸟类和哺乳动物的OASL都可以通过引入3个关键残基可逆地交换激活和放大OAS/RNase L和OASL/RIG-I系统，表明古老的OASL具有2-5A [px 5 ′A（2′p5′A）n; x = 1-3; n ≥ 2]活性，并且最近已经功能性地转换到OASL/RIG-I途径。我们的研究结果表明，在鸟类和哺乳动物的OASL分子的开关，激活和增强OAS/RNase L和OASL/RIG-I途径，响应RNA病毒感染的分子机制。
Host cells develop the OAS/RNase L [2′–5′–oligoadenylate synthetase (OAS)/ribonuclease L] system to degrade cellular and viral RNA, and/or the OASL/RIG-I (2′–5′–OAS like/retinoic acid inducible protein I) system to enhance RIG-I-mediated IFN induction, thus providing the first line of defense against viral infection. The 2′–5′–OAS-like (OASL) protein may activate the OAS/RNase L system using its typical OAS-like domain (OLD) or mimic the K63-linked pUb to enhance antiviral activity of the OASL/RIG-I system using its two tandem ubiquitin-like domains (UBLs). We first describe that divergent avian (duck and ostrich) OASL inhibit the replication of a broad range of RNA viruses by activating and magnifying the OAS/RNase L pathway in a UBL-dependent manner. This is in sharp contrast to mammalian enzymatic OASL, which activates and magnifies the OAS/RNase L pathway in a UBL-independent manner, similar to 2′–5′–oligoadenylate synthetase 1 (OAS1). We further show that both avian and mammalian OASL can reversibly exchange to activate and magnify the OAS/RNase L and OASL/RIG-I system by introducing only three key residues, suggesting that ancient OASL possess 2–5A [px5′A(2′p5′A)n; x = 1-3; n ≥ 2] activity and has functionally switched to the OASL/RIG-I pathway recently. Our findings indicate the molecular mechanisms involved in the switching of avian and mammalian OASL molecules to activate and enhance the OAS/RNase L and OASL/RIG-I pathways in response to infection by RNA viruses.
登录
查看更多内容
影响因子：
5.4
作者：
Heinecke K;Seher A;Schmitz W;Mueller TD;Sebald W;Nickel J
通讯作者：
Nickel J
影响因子：
4.5
作者：
Hancks DC;Hartley MK;Hagan C;Clark NL;Elde NC
通讯作者：
Elde NC
影响因子：
5.7
作者：
Lohoefener, Jan;Steinke, Nicola;Fedorov, Roman
通讯作者：
Fedorov, Roman
影响因子：
4.8
作者：
Sarkar, SN;Ghosh, A;Sen, GC
通讯作者：
Sen, GC
干扰素刺激的基因及其抗病毒效应子功能。
影响因子：
5.9
作者：
Schoggins, John W.;Rice, Charles M.
通讯作者：
Rice, Charles M.