Inhibition of the SREBP pathway prevents SARS-CoV-2 replication and inflammasome activation
© 2023 Soares et al..
SARS-CoV-2 induces major cellular lipid rearrangements, exploiting the host's metabolic pathways to replicate. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that control lipid metabolism. SREBP1 is associated with the regulation of fatty acids, whereas SREBP2 controls cholesterol metabolism, and both isoforms are associated with lipid droplet (LD) biogenesis. Here, we evaluated the effect of SREBP in a SARS-CoV-2-infected lung epithelial cell line (Calu-3). We showed that SARS-CoV-2 infection induced the activation of SREBP1 and SREBP2 and LD accumulation. Genetic knockdown of both SREBPs and pharmacological inhibition with the dual SREBP activation inhibitor fatostatin promote the inhibition of SARS-CoV-2 replication, cell death, and LD formation in Calu-3 cells. In addition, we demonstrated that SARS-CoV-2 induced inflammasome-dependent cell death by pyroptosis and release of IL-1β and IL-18, with activation of caspase-1, cleavage of gasdermin D1, was also reduced by SREBP inhibition. Collectively, our findings help to elucidate that SREBPs are crucial host factors required for viral replication and pathogenesis. These results indicate that SREBP is a host target for the development of antiviral strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Life science alliance - 6(2023), 11 vom: 18. Nov. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Soares, Vinicius Cardoso [VerfasserIn] |
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| Links: |
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| Themen: |
Inflammasomes |
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| Anmerkungen: |
Date Completed 07.09.2023 Date Revised 21.09.2023 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.26508/lsa.202302049 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361675305 |
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| 245 | 1 | 0 | |a Inhibition of the SREBP pathway prevents SARS-CoV-2 replication and inflammasome activation |
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| 520 | |a © 2023 Soares et al. | ||
| 520 | |a SARS-CoV-2 induces major cellular lipid rearrangements, exploiting the host's metabolic pathways to replicate. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that control lipid metabolism. SREBP1 is associated with the regulation of fatty acids, whereas SREBP2 controls cholesterol metabolism, and both isoforms are associated with lipid droplet (LD) biogenesis. Here, we evaluated the effect of SREBP in a SARS-CoV-2-infected lung epithelial cell line (Calu-3). We showed that SARS-CoV-2 infection induced the activation of SREBP1 and SREBP2 and LD accumulation. Genetic knockdown of both SREBPs and pharmacological inhibition with the dual SREBP activation inhibitor fatostatin promote the inhibition of SARS-CoV-2 replication, cell death, and LD formation in Calu-3 cells. In addition, we demonstrated that SARS-CoV-2 induced inflammasome-dependent cell death by pyroptosis and release of IL-1β and IL-18, with activation of caspase-1, cleavage of gasdermin D1, was also reduced by SREBP inhibition. Collectively, our findings help to elucidate that SREBPs are crucial host factors required for viral replication and pathogenesis. These results indicate that SREBP is a host target for the development of antiviral strategies | ||
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| 700 | 1 | |a Moreira, Isabela Batista Gonçalves |e verfasserin |4 aut | |
| 700 | 1 | |a Sacramento, Carolina Q |e verfasserin |4 aut | |
| 700 | 1 | |a Fintelman-Rodrigues, Natalia |e verfasserin |4 aut | |
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| 700 | 1 | |a Souza, Thiago Ml |e verfasserin |4 aut | |
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