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

• Published in: Frontiers in immunology 2018-06, Vol.9, p.1398-1398
• Main Authors: Rong, Enguang, Wang, Xiaoxue, Chen, Hualan, Yang, Chenghuai, Hu, Jiaxiang, Liu, Wenjie, Wang, Zeng, Chen, Xiaoyun, Zheng, Haixue, Pu, Juan, Sun, Honglei, Smith, Jacqueline, Burt, David W, Liu, Jinhua, Li, Ning, Huang, Yinhua
• Format: Article
• Language: English
• Subjects: birds; Immunology; mammals; OAS/RNase L pathway; OASL; OASL/RIG-I pathway
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.01398

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 [p 5'A(2'p5'A) ; 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.