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

作者：Elbahesh H; Jha B K; Silverman R H; Scherbik S V; Brinton M A^*

来源：Virology, 2011, 409(2): 262-270.

DOI：10.1016/j.virol.2010.10.016

• 2 '-5 ' oligoadenylate synthetase
• RNase L
• 2-5A
• Flavivirus
• RNA-protein interaction

Resistance to flavivirus-induced disease in mice is conferred by the autosomal gene Fly, 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.

• 出版日期2011-1-20