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PMID:21056894

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Citation

Elbahesh, H, Jha, BK, Silverman, RH, Scherbik, SV and Brinton, MA (2011) The Flvr-encoded murine oligoadenylate synthetase 1b (Oas1b) suppresses 2-5A synthesis in intact cells. Virology 409:262-70

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.

Links

PubMed PMC3046042 Online version:10.1016/j.virol.2010.10.016

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:OAS1A

involved_in

GO:0006164: purine nucleotide biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:OAS1A

enables

GO:0001730: 2'-5'-oligoadenylate synthetase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:OAS1A

enables

GO:0003725: double-stranded RNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:OAS1B

NOT|enables

GO:0001730: 2'-5'-oligoadenylate synthetase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:OAS1B

enables

GO:0003725: double-stranded RNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:Q78ZX0

enables

GO:0003725: double-stranded RNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:Q78ZX0

NOT|enables

GO:0001730: 2'-5'-oligoadenylate synthetase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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