Extracellular 2′-5′ Oligoadenylate Synthetase Stimulates RNase L-Independent Antiviral Activity: a Novel Mechanism of Virus-Induced Innate Immunity

• DOI: 10.1128/jvi.01003-10
• Publication Date: 2010-09-16T01:49:26Z
• Authors: Helle Kristiansen; Christina A. Scherer; Maralee McVean; Shawn P. Iadonato; Susanne Vends; Karthiga Thavache...; Thomas B. Steffensen; Kristy A. Horan; Thomas Kuri; Friedemann Weber; Søren R. Paludan; Rune Hartmann
• Keywords: 0301 basic medicine; Antiviral Agents; Immunity, Innate; Cell Line; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Virus Diseases; Endoribonucleases; Host-Pathogen Interactions; Viruses; 2',5'-Oligoadenylate Synthetase; Animals; Humans; Extracellular Space; Virus Physiological Phenomena

ABSTRACTThe 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, bothin vitroandin 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.