The Flvr-encoded murine oligoadenylate synthetase 1b (Oas1b) suppresses 2-5A synthesis in intact cells

Virology. 2011 Jan 20;409(2):262-70. doi: 10.1016/j.virol.2010.10.016. Epub 2010 Nov 5.


Resistance to flavivirus-induced disease in mice is conferred by the autosomal gene Flv, identified as 2'-5' oligoadenylate synthetase 1b (Oas1b). Resistant mice express a full-length Oas1b protein while susceptible mice express the truncated Oas1btr. In this study, Oas1b was shown to be an inactive synthetase. Although the Oas/RNase L pathway was previously shown to have an antiviral role during flavivirus infections, Oas1b protein inhibited Oas1a in vitro synthetase activity in a dose-dependent manner and reduced 2-5A production in vivo in response to poly(I:C). These findings suggest that negative regulation of 2-5A by inactive Oas1 proteins may fine tune the RNase L response that if not tightly controlled could cause significant damage in cells. The results also indicate that flavivirus resistance conferred by Oas1b is not mediated by 2-5A. Instead, Oas1b inhibits flavivirus replication by an alternative mechanism that overrides the proviral effect of reducing 2-5A accumulation and RNase L activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / metabolism*
  • Adenine Nucleotides / biosynthesis*
  • Animals
  • Endoribonucleases / biosynthesis
  • Flavivirus / growth & development*
  • Mice
  • Oligoribonucleotides / biosynthesis*


  • Adenine Nucleotides
  • Oligoribonucleotides
  • 2',5'-oligoadenylate
  • Oas1b protein, mouse
  • 2',5'-Oligoadenylate Synthetase
  • Endoribonucleases
  • 2-5A-dependent ribonuclease