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

Abstract

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.

• Authors: H Elbahesh, B K Jha, R H Silverman, S V Scherbik, M A Brinton
• Journal: Virology (Virology) Vol. 409 Issue 2 Pg. 262-70 (Jan 20 2011) ISSN: 1096-0341 [Electronic] United States
• PMID: 21056894 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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