SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein.
| العنوان: | SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein. |
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| المؤلفون: | Walter M; Buck Institute for Research on Aging, Novato, CA, United States., Chen IP; Gladstone Institutes, San Francisco, CA, United States.; University of California San Francisco, San Francisco, CA, United States., Vallejo-Gracia A; Gladstone Institutes, San Francisco, CA, United States.; University of California San Francisco, San Francisco, CA, United States., Kim IJ; Buck Institute for Research on Aging, Novato, CA, United States., Bielska O; Buck Institute for Research on Aging, Novato, CA, United States., Lam VL; University of California San Francisco, San Francisco, CA, United States., Hayashi JM; Gladstone Institutes, San Francisco, CA, United States.; University of California San Francisco, San Francisco, CA, United States., Cruz A; Buck Institute for Research on Aging, Novato, CA, United States., Shah S; Buck Institute for Research on Aging, Novato, CA, United States., Gross JD; University of California San Francisco, San Francisco, CA, United States.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, United States., Krogan NJ; Gladstone Institutes, San Francisco, CA, United States.; University of California San Francisco, San Francisco, CA, United States.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, United States.; QBI COVID-19 Research Group (QCRG), San Francisco, CA, United States., Schilling B; Buck Institute for Research on Aging, Novato, CA, United States., Ott M; Gladstone Institutes, San Francisco, CA, United States.; University of California San Francisco, San Francisco, CA, United States., Verdin E; Buck Institute for Research on Aging, Novato, CA, United States. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2022 Jan 05. Date of Electronic Publication: 2022 Jan 05. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | 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. |
| التعليقات: | Update in: PLoS Pathog. 2022 Sep 12;18(9):e1010811. (PMID: 36095012) |
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| معلومات مُعتمدة: | F31 AI164671 United States AI NIAID NIH HHS; S10 OD010786 United States OD NIH HHS; S10 OD016281 United States OD NIH HHS |
| تواريخ الأحداث: | Date Created: 20220112 Latest Revision: 20220927 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8750649 |
| DOI: | 10.1101/2022.01.04.474979 |
| PMID: | 35018374 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2022.01.04.474979 |
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