An "old" protein with a new story: Coronavirus endoribonuclease is important for evading host antiviral defenses Journal Article

Authors: Deng, X; Baker, S. C.
Article Title: An "old" protein with a new story: Coronavirus endoribonuclease is important for evading host antiviral defenses
Abstract: Here we review the evolving story of the coronavirus endoribonuclease (EndoU). Coronavirus EndoU is encoded within the sequence of nonstructural protein (nsp) 15, which was initially identified as a component of the viral replication complex. Biochemical and structural studies revealed the enzymatic nature of nsp15/EndoU, which was postulated to be essential for the unique replication cycle of viruses in the order Nidovirales. However, the role of nsp15 in coronavirus replication was enigmatic as EndoU-deficient coronaviruses were viable and replicated to near wild-type virus levels in fibroblast cells. A breakthrough in our understanding of the role of EndoU was revealed in recent studies, which showed that EndoU mediates the evasion of viral double-stranded RNA recognition by host sensors in macrophages. This new discovery of nsp15/EndoU function leads to new opportunities for investigating how a viral EndoU contributes to pathogenesis and exploiting this enzyme for therapeutics and vaccine design against pathogenic coronaviruses.
Keywords: Animals; Coronavirus; Virus Replication; interferon; endoribonuclease; nsp15; Coronavirus/enzymology; Coronavirus Infections/immunology; Endoribonucleases/metabolism; Gene Expression Regulation, Viral/physiology; Viral Nonstructural Proteins; Antiviral defense; Double-stranded RNA; Host recognition
Journal Title: Virology
Volume: 517
ISSN: 1096-0341; 0042-6822
Publisher: Elsevier Inc  
Journal Place: United States
Date Published: 2018
Start Page: 157
End Page: 163
Language: eng
Notes: LR: 20180420; CI: Copyright (c) 2018; GR: R01 AI085089/AI/NIAID NIH HHS/United States; JID: 0110674; 0 (Viral Nonstructural Proteins); EC 3.1.- (Endoribonucleases); NIHMS932488; OTO: NOTNLM; PMCR: 2019/04/01 00:00; 2017/10/04 00:00 [received]; 2017/12/21 00:00 [revised]; 2017/12/22 00:00 [accepted]; 2019/04/01 00:00 [pmc-release]; 2018/01/09 06:00 [pubmed]; 2018/04/21 06:00 [medline]; 2018/01/09 06:00 [entrez]; ppublish