Molecular mechanisms for the adaptive switching between the OAS/RNase L and OASL/RIG-I pathways in birds and mammals: Adaptive exchanging of the OAS/RNase L and OASL/RIG-I pathway

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

Research output: Contribution to journalArticlepeer-review

Abstract

Host cells develop the OAS/RNase L (2-5 oligoadenylate synthetase/ribonuclease L) system to degrade cellular and viral RNA, and/or the OASL/RIG-I (2-5 oligoadenylate synthetase 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 oligoadenylate synthetase 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 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
Original languageEnglish
Article number1398
JournalFrontiers in Immunology
Volume9
DOIs
Publication statusPublished - 20 Jun 2018

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