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Resurrection of 2′-5′-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication
The prenylated form of the human 2′-5′-oligoadenylate synthetase 1 (OAS1) protein has been shown to potently inhibit the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. However, the OAS1 ortholog...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683996/ https://www.ncbi.nlm.nih.gov/pubmed/38015855 http://dx.doi.org/10.1371/journal.pbio.3002398 |
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author | Lytras, Spyros Wickenhagen, Arthur Sugrue, Elena Stewart, Douglas G. Swingler, Simon Sims, Anna Jackson Ireland, Hollie Davies, Emma L. Ludlam, Eliza M. Li, Zhuonan Hughes, Joseph Wilson, Sam J. |
author_facet | Lytras, Spyros Wickenhagen, Arthur Sugrue, Elena Stewart, Douglas G. Swingler, Simon Sims, Anna Jackson Ireland, Hollie Davies, Emma L. Ludlam, Eliza M. Li, Zhuonan Hughes, Joseph Wilson, Sam J. |
author_sort | Lytras, Spyros |
collection | PubMed |
description | The prenylated form of the human 2′-5′-oligoadenylate synthetase 1 (OAS1) protein has been shown to potently inhibit the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. However, the OAS1 orthologue in the horseshoe bats (superfamily Rhinolophoidea), the reservoir host of SARS-related coronaviruses (SARSr-CoVs), has lost the prenylation signal required for this antiviral activity. Herein, we used an ancestral state reconstruction approach to predict and reconstitute in vitro, the most likely OAS1 protein sequence expressed by the Rhinolophoidea common ancestor prior to its prenylation loss (RhinoCA OAS1). We exogenously expressed the ancient bat protein in vitro to show that, unlike its non-prenylated horseshoe bat descendants, RhinoCA OAS1 successfully blocks SARS-CoV-2 replication. Using protein structure predictions in combination with evolutionary hypothesis testing methods, we highlight sites under unique diversifying selection specific to OAS1’s evolution in the Rhinolophoidea. These sites are located near the RNA-binding region and the C-terminal end of the protein where the prenylation signal would have been. Our results confirm that OAS1 prenylation loss at the base of the Rhinolophoidea clade ablated the ability of OAS1 to restrict SARSr-CoV replication and that subsequent evolution of the gene in these bats likely favoured an alternative function. These findings can advance our understanding of the tightly linked association between SARSr-CoVs and horseshoe bats. |
format | Online Article Text |
id | pubmed-10683996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-106839962023-11-30 Resurrection of 2′-5′-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication Lytras, Spyros Wickenhagen, Arthur Sugrue, Elena Stewart, Douglas G. Swingler, Simon Sims, Anna Jackson Ireland, Hollie Davies, Emma L. Ludlam, Eliza M. Li, Zhuonan Hughes, Joseph Wilson, Sam J. PLoS Biol Short Reports The prenylated form of the human 2′-5′-oligoadenylate synthetase 1 (OAS1) protein has been shown to potently inhibit the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. However, the OAS1 orthologue in the horseshoe bats (superfamily Rhinolophoidea), the reservoir host of SARS-related coronaviruses (SARSr-CoVs), has lost the prenylation signal required for this antiviral activity. Herein, we used an ancestral state reconstruction approach to predict and reconstitute in vitro, the most likely OAS1 protein sequence expressed by the Rhinolophoidea common ancestor prior to its prenylation loss (RhinoCA OAS1). We exogenously expressed the ancient bat protein in vitro to show that, unlike its non-prenylated horseshoe bat descendants, RhinoCA OAS1 successfully blocks SARS-CoV-2 replication. Using protein structure predictions in combination with evolutionary hypothesis testing methods, we highlight sites under unique diversifying selection specific to OAS1’s evolution in the Rhinolophoidea. These sites are located near the RNA-binding region and the C-terminal end of the protein where the prenylation signal would have been. Our results confirm that OAS1 prenylation loss at the base of the Rhinolophoidea clade ablated the ability of OAS1 to restrict SARSr-CoV replication and that subsequent evolution of the gene in these bats likely favoured an alternative function. These findings can advance our understanding of the tightly linked association between SARSr-CoVs and horseshoe bats. Public Library of Science 2023-11-28 /pmc/articles/PMC10683996/ /pubmed/38015855 http://dx.doi.org/10.1371/journal.pbio.3002398 Text en © 2023 Lytras et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Short Reports Lytras, Spyros Wickenhagen, Arthur Sugrue, Elena Stewart, Douglas G. Swingler, Simon Sims, Anna Jackson Ireland, Hollie Davies, Emma L. Ludlam, Eliza M. Li, Zhuonan Hughes, Joseph Wilson, Sam J. Resurrection of 2′-5′-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication |
title | Resurrection of 2′-5′-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication |
title_full | Resurrection of 2′-5′-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication |
title_fullStr | Resurrection of 2′-5′-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication |
title_full_unstemmed | Resurrection of 2′-5′-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication |
title_short | Resurrection of 2′-5′-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication |
title_sort | resurrection of 2′-5′-oligoadenylate synthetase 1 (oas1) from the ancestor of modern horseshoe bats blocks sars-cov-2 replication |
topic | Short Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683996/ https://www.ncbi.nlm.nih.gov/pubmed/38015855 http://dx.doi.org/10.1371/journal.pbio.3002398 |
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