Article ; Online: Endomembrane targeting of human OAS1 p46 augments antiviral activity.
2021 Volume 10
Abstract: ... synthetase 1, OAS1 p46, is prenylated and targeted to the endomembrane system. Membrane localization of OAS1 ... p46 confers enhanced access to viral replication sites and results in increased antiviral activity ... Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense RNA generated ...
| Abstract | Many host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shields viral products from cellular innate immune sensors. Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense RNA generated by viruses that use these compartments for replication. Here, we reveal that an isoform of oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted to the endomembrane system. Membrane localization of OAS1 p46 confers enhanced access to viral replication sites and results in increased antiviral activity against a subset of RNA viruses including flaviviruses, picornaviruses, and SARS-CoV-2. Finally, our human genetic analysis shows that the |
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| MeSH term(s) | 2',5'-Oligoadenylate Synthetase/metabolism ; Animals ; COVID-19/immunology ; COVID-19/virology ; CRISPR-Cas Systems ; Cell Line ; Gene Editing ; Humans ; Polymorphism, Single Nucleotide ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/metabolism |
| Chemical Substances | OAS1 protein, human (EC 2.7.7.-) ; 2',5'-Oligoadenylate Synthetase (EC 2.7.7.84) |
| Language | English |
| Publishing date | 2021-08-03 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2687154-3 |
| ISSN | 2050-084X ; 2050-084X |
| ISSN (online) | 2050-084X |
| ISSN | 2050-084X |
| DOI | 10.7554/eLife.71047 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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