title: Viral phosphodiesterases that antagonize double-stranded RNA signaling to RNase L by degrading 2-5A.
abstract: The host interferon (IFN) antiviral response involves a myriad of diverse biochemical pathways that disrupt virus replication cycles at many different levels. As a result, viruses have acquired and evolved genes that antagonize the host antiviral proteins. IFNs inhibit viral infections in part through the 2',5'-oligoadenylate (2-5A) synthetase (OAS)/RNase L pathway. OAS proteins are pathogen recognition receptors that exist at different basal levels in different cell types and that are IFN inducible. Upon activation by the pathogen-associated molecular pattern viral double-stranded RNA, certain OAS proteins synthesize 2-5A from ATP. 2-5A binds to the antiviral enzyme RNase L causing its dimerization and activation. Recently, disparate RNA viruses, group 2a betacoronaviruses, and group A rotaviruses, have been shown to produce proteins with 2',5'-phosphodiesterase (PDE) activities that eliminate 2-5A thereby evading the antiviral activity of the OAS/RNase L pathway. These viral proteins are members of the eukaryotic-viral LigT-like group of 2H phosphoesterases, so named for the presence of 2 conserved catalytic histidine residues. Here, we will review the biochemistry, biology, and implications of viral and cellular 2',5'-PDEs that degrade 2-5A. In addition, we discuss alternative viral and cellular strategies for limiting the activity of OAS/RNase L.
authors.affiliation: 1 Department of Cancer Biology, Lerner Research Institute , Cleveland Clinic, Cleveland, Ohio.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Silverman
authors.forename: Susan R
authors.initials: SR
authors.lastname: Weiss
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D000818:Animals; D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000378:metabolism*; D015398:Signal Transduction; D014780:Viruses / Q000201:enzymology* / Q000378:metabolism
chemical_list: D012330:RNA, Double-Stranded; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D010727:Phosphoric Diester Hydrolases