title: Rapid Uptake and Inhibition of Viral Propagation by Extracellular OAS1.
abstract: The oligoadenylate synthetase (OAS) proteins are traditionally considered intracellular antiviral proteins that mediate antiviral activity through the synthesis of 2'-5'-linked oligoadenylates and subsequent activation of the endoribonuclease RNase L. However, we have recently demonstrated that exogenous recombinant OAS1 is taken up by cells and reduces viral replication both in cell culture and in vivo, independent of RNase L. These results demonstrate a novel paracrine antiviral activity of OAS working in parallel with the classical RNase L pathway. In this study, we investigate the uptake kinetics of recombinant porcine OAS1 and show that it is rapidly and efficiently internalized in a manner that can be blocked by heparin. Heparin, furthermore, abolishes the antiviral activity of OAS1, demonstrating the requirement of the intracellular localization of OAS1 to inhibit the virus. In addition, we demonstrate that exogenous OAS1 affects an early step of the viral replication cycle.
authors.affiliation: 1 Department of Molecular Biology and Genetics, Centre for Structural Biology, Aarhus University , Aarhus, Denmark .
authors.forename: Karthiga
authors.initials: K
authors.lastname: Thavachelvam
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Gad
authors.forename: Mikkel Søes
authors.initials: MS
authors.lastname: Ibsen
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprès
authors.forename: Marianne
authors.initials: M
authors.lastname: Hokland
authors.forename: Rune
authors.initials: R
authors.lastname: Hartmann
authors.forename: Helle
authors.initials: H
authors.lastname: Kristiansen
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004686:Encephalomyocarditis virus / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space; D006367:HeLa Cells; D006493:Heparin / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D021381:Protein Transport; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013552:Swine; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011994:Recombinant Proteins; D006493:Heparin; D015088:2',5'-Oligoadenylate Synthetase