Molecular Mechanisms for the Adaptive Switching Between the OAS/RNase L and OASL/RIG-I Pathways in Birds and Mammals

文献类型： 外文期刊

第一作者： Rong, Enguang

作者： Rong, Enguang;Wang, Xiaoxue;Hu, Jiaxiang;Liu, Wenjie;Li, Ning;Huang, Yinhua;Chen, Hualan;Wang, Zeng;Chen, Hualan;Wang, Zeng;Yang, Chenghuai;Chen, Xiaoyun;Zheng, Haixue;Zheng, Haixue;Pu, Juan;Sun, Honglei;Liu, Jinhua;Smith, Jacqueline;Burt, David W.;Smith, Jacqueline;Burt, David W.

作者机构：

关键词： birds; mammals; OASL; OAS/RNase L pathway; OASL/RIG-I pathway

期刊名称：FRONTIERS IN IMMUNOLOGY （ 影响因子：7.561； 五年影响因子：7.624 ）

ISSN： 1664-3224

年卷期： 2018 年 9 卷

页码：

收录情况： SCI

摘要： 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.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序