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Lipid droplets fuels SARS-CoV-2 replication and inflammatory response

Suelen da Silva Gomes Dias, Vinicius Cardoso Soares, André C. Ferreira, Carolina Q. Sacramento, Natalia Fintelman-Rodrigues, Jairo R. Temerozo, Lívia Teixeira, Ester Barreto, Mayara Mattos, Caroline S. de Freitas, Isaclaudia G. Azevedo-Quintanilha, Pedro Paulo A. Manso, Eugenio D. Hottz, Camila R. R. Pão, Dumith C. Bou-Habib, Fernando A. Bozza, Thiago M. L. Souza, View ORCID ProfilePatrícia T. Bozza
doi: https://doi.org/10.1101/2020.08.22.262733
Suelen da Silva Gomes Dias
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
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Vinicius Cardoso Soares
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
2Program of Immunology and Inflammation, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil
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André C. Ferreira
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
3National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDNP), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil
4Universidade Iguaçu, Nova Iguaçu, RJ, Brazil
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Carolina Q. Sacramento
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
3National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDNP), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil
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Natalia Fintelman-Rodrigues
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
3National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDNP), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil
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Jairo R. Temerozo
5Laboratory on Thymus Research, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
6National Institute for Science and Technology on Neuroimmunomodulation (INCT/NIM), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, RJ, Brazil
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Lívia Teixeira
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
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Ester Barreto
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
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Mayara Mattos
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
3National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDNP), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil
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Caroline S. de Freitas
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
3National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDNP), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil
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Isaclaudia G. Azevedo-Quintanilha
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
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Pedro Paulo A. Manso
7Laboratory of Patology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
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Eugenio D. Hottz
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
8Laboratory of Immunothrombosis, Department of Biochemistry, Federal University of Juiz de Fora (UFJF), Juiz de Fora, MG, Brazil
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Camila R. R. Pão
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
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Dumith C. Bou-Habib
5Laboratory on Thymus Research, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
6National Institute for Science and Technology on Neuroimmunomodulation (INCT/NIM), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, RJ, Brazil
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Fernando A. Bozza
9National Institute of Infectology (INI), FIOCRUZ, Rio de Janeiro, Brazil
10D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
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Thiago M. L. Souza
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
3National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDNP), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil
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Patrícia T. Bozza
1Laboratory of Immunopharmacology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, RJ, Brazil
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  • ORCID record for Patrícia T. Bozza
  • For correspondence: pbozza@ioc.fiocruz.br pbozza@gmail.com
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Abstract

Viruses are obligate intracellular parasites that make use of the host metabolic machineries to meet their biosynthetic needs, identifying the host pathways essential for the virus replication may lead to potential targets for therapeutic intervention. The mechanisms and pathways explored by SARS-CoV-2 to support its replication within host cells are not fully known. Lipid droplets (LD) are organelles with major functions in lipid metabolism and energy homeostasis, and have multiple roles in infections and inflammation. Here we demonstrate that monocytes from COVID-19 patients have an increased LD accumulation compared to SARS-CoV-2 negative donors. In vitro, SARS-CoV-2 infection modulates pathways of lipid synthesis and uptake, as CD36, SREBP-1, PPARγ and DGAT-1 in human monocytes and triggered LD formation in different human cells. LDs were found in close apposition with SARS-CoV-2 proteins and double-stranded (ds)-RNA. The pharmacological modulation of LD formation by inhibition of DGAT-1 with A922500 significantly inhibited SARS-CoV-2 replication as well as reduced production of pro-inflammatory mediators. Taken together, we demonstrate the essential role of lipid metabolic reprograming and LD formation in SARS-CoV-2 replication and pathogenesis, opening new opportunities for therapeutic strategies to COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 23, 2020.
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Lipid droplets fuels SARS-CoV-2 replication and inflammatory response
Suelen da Silva Gomes Dias, Vinicius Cardoso Soares, André C. Ferreira, Carolina Q. Sacramento, Natalia Fintelman-Rodrigues, Jairo R. Temerozo, Lívia Teixeira, Ester Barreto, Mayara Mattos, Caroline S. de Freitas, Isaclaudia G. Azevedo-Quintanilha, Pedro Paulo A. Manso, Eugenio D. Hottz, Camila R. R. Pão, Dumith C. Bou-Habib, Fernando A. Bozza, Thiago M. L. Souza, Patrícia T. Bozza
bioRxiv 2020.08.22.262733; doi: https://doi.org/10.1101/2020.08.22.262733
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Lipid droplets fuels SARS-CoV-2 replication and inflammatory response
Suelen da Silva Gomes Dias, Vinicius Cardoso Soares, André C. Ferreira, Carolina Q. Sacramento, Natalia Fintelman-Rodrigues, Jairo R. Temerozo, Lívia Teixeira, Ester Barreto, Mayara Mattos, Caroline S. de Freitas, Isaclaudia G. Azevedo-Quintanilha, Pedro Paulo A. Manso, Eugenio D. Hottz, Camila R. R. Pão, Dumith C. Bou-Habib, Fernando A. Bozza, Thiago M. L. Souza, Patrícia T. Bozza
bioRxiv 2020.08.22.262733; doi: https://doi.org/10.1101/2020.08.22.262733

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