title: Extracellular 2'-5' oligoadenylate synthetase stimulates RNase L-independent antiviral activity: a novel mechanism of virus-induced innate immunity.
abstract: The 2'-5' oligoadenylate synthetase (OAS) proteins are traditionally considered intracellular antiviral proteins. However, several studies demonstrate a correlation between the concentration of freely circulating OAS protein in sera from hepatitis C patients and their clinical prognosis. Here we demonstrate that extracellular OAS1 enters into cells and possesses a strong antiviral activity, both in vitro and in vivo, which is independent of RNase L. The OAS protein directly inhibits viral proliferation and does not require the activation of known antiviral signaling pathways. We propose that OAS produced by cells infected with viruses is released to the extracellular space, where it acts as a paracrine antiviral agent. Thus, the OAS protein represents the first direct antiviral compound released by virus-infected cells.
authors.affiliation: Department of Molecular Biology, Aarhus University, Gustav Wieds vej 10c, Aarhus, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Kristiansen
authors.forename: Christina A
authors.initials: CA
authors.lastname: Scherer
authors.forename: Maralee
authors.initials: M
authors.lastname: McVean
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Iadonato
authors.forename: Susanne
authors.initials: S
authors.lastname: Vends
authors.forename: Karthiga
authors.initials: K
authors.lastname: Thavachelvam
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Steffensen
authors.forename: Kristy A
authors.initials: KA
authors.lastname: Horan
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuri
authors.forename: Friedemann
authors.initials: F
authors.lastname: Weber
authors.forename: Søren R
authors.initials: SR
authors.lastname: Paludan
authors.forename: Rune
authors.initials: R
authors.lastname: Hartmann
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000998:Antiviral Agents / Q000276:immunology*; D002460:Cell Line; D004722:Endoribonucleases / Q000235:genetics / Q000276:immunology*; D005110:Extracellular Space / Q000201:enzymology* / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D014777:Virus Diseases / Q000201:enzymology* / Q000276:immunology* / Q000821:virology; D018406:Virus Physiological Phenomena; D014780:Viruses / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease