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SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein
SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a p...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750649/ https://www.ncbi.nlm.nih.gov/pubmed/35018374 http://dx.doi.org/10.1101/2022.01.04.474979 |
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author | Walter, Marius Chen, Irene P Vallejo-Gracia, Albert Kim, Ik-Jung Bielska, Olga Lam, Victor L Hayashi, Jennifer M Cruz, Andrew Shah, Samah Gross, John D Krogan, Nevan J Schilling, Birgit Ott, Melanie Verdin, Eric |
author_facet | Walter, Marius Chen, Irene P Vallejo-Gracia, Albert Kim, Ik-Jung Bielska, Olga Lam, Victor L Hayashi, Jennifer M Cruz, Andrew Shah, Samah Gross, John D Krogan, Nevan J Schilling, Birgit Ott, Melanie Verdin, Eric |
author_sort | Walter, Marius |
collection | PubMed |
description | SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD-dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 stably interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions. |
format | Online Article Text |
id | pubmed-8750649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-87506492022-01-12 SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein Walter, Marius Chen, Irene P Vallejo-Gracia, Albert Kim, Ik-Jung Bielska, Olga Lam, Victor L Hayashi, Jennifer M Cruz, Andrew Shah, Samah Gross, John D Krogan, Nevan J Schilling, Birgit Ott, Melanie Verdin, Eric bioRxiv Article SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD-dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 stably interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions. Cold Spring Harbor Laboratory 2022-01-05 /pmc/articles/PMC8750649/ /pubmed/35018374 http://dx.doi.org/10.1101/2022.01.04.474979 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Walter, Marius Chen, Irene P Vallejo-Gracia, Albert Kim, Ik-Jung Bielska, Olga Lam, Victor L Hayashi, Jennifer M Cruz, Andrew Shah, Samah Gross, John D Krogan, Nevan J Schilling, Birgit Ott, Melanie Verdin, Eric SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein |
title | SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein |
title_full | SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein |
title_fullStr | SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein |
title_full_unstemmed | SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein |
title_short | SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein |
title_sort | sirt5 is a proviral factor that interacts with sars-cov-2 nsp14 protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750649/ https://www.ncbi.nlm.nih.gov/pubmed/35018374 http://dx.doi.org/10.1101/2022.01.04.474979 |
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