SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner

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Saccon, Tatiana Dandolini ; Mousovich-Neto, Felippe ; Ludwig, Raissa Guimaraes ; Carregari, Victor Corasolla ; dos Anjos Souza, Ana Beatriz ; dos Passos, Amanda Stephane Cruz ; Martini, Matheus Cavalheiro ; Barbosa, Priscilla Paschoal ; de Souza, Gabriela Fabiano ; Muraro, Stefanie Primon ; Forato, Julia ; Amorim, Mariene Ribeiro ; Marques, Rafael Elias ; Veras, Flavio Protasio ; Barreto, Ester ; Goncalves, Tiago Tomazini ; Paiva, Isadora Marques ; Fazolini, Narayana P. B. ; Onodera, Carolina Mie Kawagosi ; Martins Junior, Ronaldo Braganca ; de Araujo, Paulo Henrique Cavalcanti ; Batah, Sabrina Setembre ; Viana, Rosa Maria Mendes ; de Melo, Danilo Machado ; Fabro, Alexandre Todorovic ; Arruda, Eurico ; Queiroz Cunha, Fernando ; Cunha, Thiago Mattar ; Pretti, Marco Antonio M. ; Smith, Bradley Joseph ; Marques-Souza, Henrique ; Knittel, Thiago L. ; Ruiz, Gabriel Palermo ; Profeta, Gerson S. ; Fontes-Cal, Tereza Cristina Minto ; Boroni, Mariana ; Vinolo, Marco Aurelio Ramirez ; Farias, Alessandro S. ; Moraes-Vieira, Pedro Manoel M. ; Bizzacchi, Joyce Maria Annichino ; Teesalu, Tambet ; Chaim, Felipe David Mendonca ; Cazzo, Everton ; Chaim, Elinton Adami ; Proenca-Modena, Jose Luiz ; Martins-de-Souza, Daniel ; Osako, Mariana Kiomy ; Leiria, Luiz Osorio ; Mori, Marcelo A.

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 13, n. 1, p. 15-pg., 2022-09-29.

Abstract

Visceral adiposity is a risk factor for severe COVID-19, and infection of adipose tissue by SARS-CoV-2 has been reported. Here the authors confirm that human adipose tissue is a possible site for SARS-CoV-2 infection, but the degree of adipose tissue infection and the way adipocytes respond to the virus depend on the adipose tissue depot and the viral strain. Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage. Visceral fat cells express more ACE2 and are more susceptible to SARS-CoV-2 infection than their subcutaneous counterparts. SARS-CoV-2 infection leads to inhibition of lipolysis in subcutaneous fat cells, while in visceral fat cells, it results in higher expression of pro-inflammatory cytokines. Viral load and cellular response are attenuated when visceral fat cells are infected with the SARS-CoV-2 gamma variant. A similar degree of cell death occurs 4-days after SARS-CoV-2 infection, regardless of the cell origin or viral lineage. Hence, SARS-CoV-2 infects human fat cells, replicating and altering cell function and viability in a depot- and viral lineage-dependent fashion. (AU)

• FAPESP's process: 20/08716-9 - Using pre-clinical models to determine molecular candidates that contribute to the higher risk of COVID-19 during aging
• Grantee: Tatiana Dandolini Saccon
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/04558-0 - Characterization of intrinsic risk factors and the development of new diagnostic and treatment alternatives for COVID-19
• Grantee: José Luiz Proença Módena
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/05155-9 - The role of the glycoproteome and phosphoproteome during neuronal differentiation in schizophrenia
• Grantee: Victor Corasolla Carregari
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/10373-5 - Using pre-clinical models to determine molecular candidates that contribute to the higher risk of COVID-19 during aging
• Grantee: Felippe Mousovich Neto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/04919-2 - Determining molecular candidates that contribute to the higher risk of COVID-19 in aged individuals
• Grantee: Marcelo Alves da Silva Mori
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/04746-0 - Understanding the molecular bases and the role of risk factors associated to SARS-CoV-2 infection in preclinical models
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics
• Grantee: Marcelo Alves da Silva Mori
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/23920-9 - Varredura e caracterização de moléculas circulantes que afetam o gasto energético
• Grantee: Raissa Guimarães Ludwig
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/24163-4 - Screening and characterization of fluoroquinolone compounds and their influence on the biogenesis of miRNAs
• Grantee: Gerson Profeta de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/00194-8 - Pathogenesis and neurovirulence of emerging viruses in Brazil
• Grantee: José Luiz Proença Módena
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/21635-8 - Study of the role of miR-203-3p in adipose tissue metabolism and in the pathogenesis of metabolic diseases in mice
• Grantee: Gabriel Palermo Ruiz
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/00098-7 - Multi-User Equipment approved in grant 2017/25588-1: cromatógrafo Acquity UPLC I-Class
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 20/05040-4 - Translational study on the role of specialised pro-resolving lipid mediators in the tolerance against CARS-CoV-2 infection
• Grantee: Luiz Osório Silveira Leiria
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/08264-8 - Investigation on the mechanisms underlying brown adipose tissue/liver crosstalk for the regulation of hepatic de novo lipogenesis and glucose production
• Grantee: Luiz Osório Silveira Leiria
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/04579-7 - Study of the risk factors associated with greater severity to COVID-19 and mapping of the metabolic pathways required for the anti-SARS-CoV-2 response
• Grantee: Pedro Manoel Mendes de Moraes Vieira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/26119-0 - Emerging and re-emerging viruses: biology, pathogenesis and prospection
• Grantee: Eurico de Arruda Neto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/04726-2 - Investigation of new tissue-specific mechanisms of aging control by caloric restriction in C. elegans
• Grantee: Thiago Leite Knittel
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/04583-4 - Impact of intestinal microbiota and its metabolites on SARS-CoV-2 infection
• Grantee: Marco Aurélio Ramirez Vinolo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/15959-5 - RANK-RANKL signaling in skeletal muscle mitochondrial dynamics
• Grantee: Mariana Kiomy Osako
• Support Opportunities: Regular Research Grants