Oligoadenylate synthetase 1 displays dual antiviral mechanisms in driving translational shutdown and protecting interferon production.

Autor:	Harioudh MK; Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, Pittsburgh, PA, USA., Perez J; Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, Pittsburgh, PA, USA., Chong Z; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA., Nair S; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA., So L; Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA; Division of Immunology, Benaroya Research Institute, Seattle, WA, USA., McCormick KD; Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, Pittsburgh, PA, USA., Ghosh A; Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, Pittsburgh, PA, USA., Shao L; Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, Pittsburgh, PA, USA., Srivastava R; Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, Pittsburgh, PA, USA., Soveg F; Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA., Ebert TS; Department of Biochemistry, Ludwig Maximilians Universität, Munich, Germany., Atianand MK; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Hornung V; Department of Biochemistry, Ludwig Maximilians Universität, Munich, Germany., Savan R; Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA., Diamond MS; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA., Sarkar SN; Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: saumen@pitt.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2024 Mar 12; Vol. 57 (3), pp. 446-461.e7. Date of Electronic Publication: 2024 Feb 28.
DOI:	10.1016/j.immuni.2024.02.002
Abstrakt:	In response to viral infection, how cells balance translational shutdown to limit viral replication and the induction of antiviral components like interferons (IFNs) is not well understood. Moreover, how distinct isoforms of IFN-induced oligoadenylate synthetase 1 (OAS1) contribute to this antiviral response also requires further elucidation. Here, we show that human, but not mouse, OAS1 inhibits SARS-CoV-2 replication through its canonical enzyme activity via RNase L. In contrast, both mouse and human OAS1 protect against West Nile virus infection by a mechanism distinct from canonical RNase L activation. OAS1 binds AU-rich elements (AREs) of specific mRNAs, including IFNβ. This binding leads to the sequestration of IFNβ mRNA to the endomembrane regions, resulting in prolonged half-life and continued translation. Thus, OAS1 is an ARE-binding protein with two mechanisms of antiviral activity: driving inhibition of translation but also a broader, non-canonical function of protecting IFN expression from translational shutdown. Competing Interests: Declaration of interests M.S.D. is a consultant for Inbios, Journal of Virol. Biotechnology, Ocugen, Topspin, Moderna, and Merck. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Journal of Virol. Biotechnology, Emergent BioSolutions, and Moderna. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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