The Flvr-encoded murine oligoadenylate synthetase 1b (Oas1b) suppresses 2-5A synthesis in intact cells |
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Authors: | Elbahesh H Jha B K Silverman R H Scherbik S V Brinton M A |
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Affiliation: | a Department of Biology, Georgia State University, Atlanta, GA, USAb Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA |
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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. |
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Keywords: | 2&prime -5&prime oligoadenylate synthetase RNase L 2-5A Flavivirus RNA-protein interaction |
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