Extracellular 2'-5' oligoadenylate synthetase stimulates RNase L-independent antiviral activity: a novel mechanism of virus-induced innate immunity.
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.
Kristiansen
Helle
H
Department of Molecular Biology, Aarhus University, Gustav Wieds vej 10c, Aarhus, Denmark.
Scherer
Christina A
CA
McVean
Maralee
M
Iadonato
Shawn P
SP
Vends
Susanne
S
Thavachelvam
Karthiga
K
Steffensen
Thomas B
TB
Horan
Kristy A
KA
Kuri
Thomas
T
Weber
Friedemann
F
Paludan
Søren R
SR
Hartmann
Rune
R
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*
D000998:Antiviral Agents; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease