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

Husni Elbahesh, B. K. Jha, R. H. Silverman, S. V. Scherbik, M. A. Brinton

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)262-270
Number of pages9
JournalVirology
Volume409
Issue number2
DOIs
StatePublished - Jan 20 2011

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Ligases
Flavivirus
Flavivirus Infections
Proteins
2',5'-oligoadenylate
Antiviral Agents
Genes
2-5A-dependent ribonuclease

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

Elbahesh, H., Jha, B. K., Silverman, R. H., Scherbik, S. V., & Brinton, M. A. (2011). The Flvr-encoded murine oligoadenylate synthetase 1b (Oas1b) suppresses 2-5A synthesis in intact cells. Virology, 409(2), 262-270. https://doi.org/10.1016/j.virol.2010.10.016

The Flvr-encoded murine oligoadenylate synthetase 1b (Oas1b) suppresses 2-5A synthesis in intact cells. / Elbahesh, Husni; Jha, B. K.; Silverman, R. H.; Scherbik, S. V.; Brinton, M. A.

In: Virology, Vol. 409, No. 2, 20.01.2011, p. 262-270.

Research output: Contribution to journalArticle

Elbahesh, H, Jha, BK, Silverman, RH, Scherbik, SV & Brinton, MA 2011, 'The Flvr-encoded murine oligoadenylate synthetase 1b (Oas1b) suppresses 2-5A synthesis in intact cells', Virology, vol. 409, no. 2, pp. 262-270. https://doi.org/10.1016/j.virol.2010.10.016
Elbahesh, Husni ; Jha, B. K. ; Silverman, R. H. ; Scherbik, S. V. ; Brinton, M. A. / The Flvr-encoded murine oligoadenylate synthetase 1b (Oas1b) suppresses 2-5A synthesis in intact cells. In: Virology. 2011 ; Vol. 409, No. 2. pp. 262-270.
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