دورية أكاديمية
أعرض في EDS

SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein.

التفاصيل البيبلوغرافية
العنوان: SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein.
المؤلفون: Walter M; Buck Institute for Research on Aging, Novato, California, United States of America., Chen IP; Gladstone Institutes, San Francisco, California, United States of America.; University of California San Francisco, San Francisco, California, United States of America.; QBI COVID-19 Research Group (QCRG), San Francisco, California, United States of America., Vallejo-Gracia A; Gladstone Institutes, San Francisco, California, United States of America.; University of California San Francisco, San Francisco, California, United States of America.; QBI COVID-19 Research Group (QCRG), San Francisco, California, United States of America., Kim IJ; Buck Institute for Research on Aging, Novato, California, United States of America., Bielska O; Buck Institute for Research on Aging, Novato, California, United States of America., Lam VL; University of California San Francisco, San Francisco, California, United States of America., Hayashi JM; Gladstone Institutes, San Francisco, California, United States of America.; University of California San Francisco, San Francisco, California, United States of America.; QBI COVID-19 Research Group (QCRG), San Francisco, California, United States of America., Cruz A; Buck Institute for Research on Aging, Novato, California, United States of America., Shah S; Buck Institute for Research on Aging, Novato, California, United States of America., Soveg FW; Gladstone Institutes, San Francisco, California, United States of America.; University of California San Francisco, San Francisco, California, United States of America.; QBI COVID-19 Research Group (QCRG), San Francisco, California, United States of America., Gross JD; University of California San Francisco, San Francisco, California, United States of America.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, California, United States of America., Krogan NJ; Gladstone Institutes, San Francisco, California, United States of America.; University of California San Francisco, San Francisco, California, United States of America.; QBI COVID-19 Research Group (QCRG), San Francisco, California, United States of America.; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, California, United States of America., Jerome KR; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, United States of America.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, United States of America., Schilling B; Buck Institute for Research on Aging, Novato, California, United States of America., Ott M; Gladstone Institutes, San Francisco, California, United States of America.; University of California San Francisco, San Francisco, California, United States of America.; QBI COVID-19 Research Group (QCRG), San Francisco, California, United States of America.; Chan Zuckerberg Biohub, San Francisco, California, United States of America., Verdin E; Buck Institute for Research on Aging, Novato, California, United States of America.
المصدر: PLoS pathogens [PLoS Pathog] 2022 Sep 12; Vol. 18 (9), pp. e1010811. Date of Electronic Publication: 2022 Sep 12 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: COVID-19* , Sirtuins*/genetics, Antiviral Agents ; Exoribonucleases/metabolism ; Humans ; Lysine ; Methyltransferases/metabolism ; NAD ; Proviruses ; RNA, Viral/metabolism ; SARS-CoV-2 ; Viral Nonstructural Proteins/metabolism
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 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, independently of the Mitochondrial Antiviral Signaling Protein MAVS. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions.
Competing Interests: The Krogan Laboratory has received research support from Vir Biotechnology, F. Hoffmann-La Roche, and Rezo Therapeutics. Nevan J. Krogan has financially compensated consulting agreements with the Icahn School of Medicine at Mount Sinai, New York, Maze Therapeutics, Interline Therapeutics, Rezo Therapeutics, GEn1E Lifesciences, Inc. and Twist Bioscience Corp. He is on the Board of Directors of Rezo Therapeutics and is a shareholder in Tenaya Therapeutics, Maze Therapeutics, Rezo Therapeutics, and Interline Therapeutics.
التعليقات: Update of: bioRxiv. 2022 Jan 05;:. (PMID: 35018374)
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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
المشرفين على المادة: 0 (Antiviral Agents)
0 (RNA, Viral)
0 (Viral Nonstructural Proteins)
0U46U6E8UK (NAD)
EC 2.1.1.- (Methyltransferases)
EC 3.1.- (Exoribonucleases)
EC 3.5.1.- (SIRT5 protein, human)
EC 3.5.1.- (Sirtuins)
K3Z4F929H6 (Lysine)
تواريخ الأحداث: Date Created: 20220912 Date Completed: 20220926 Latest Revision: 20240216
رمز التحديث: 20240216
مُعرف محوري في PubMed: PMC9499238
DOI: 10.1371/journal.ppat.1010811
PMID: 36095012
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1010811