eLife (Jul 2023)
SARS-CoV-2 uses CD4 to infect T helper lymphocytes
- Natalia S Brunetti,
- Gustavo G Davanzo,
- Diogo de Moraes,
- Allan JR Ferrari,
- Gabriela F Souza,
- Stéfanie Primon Muraro,
- Thiago L Knittel,
- Vinicius O Boldrini,
- Lauar B Monteiro,
- João Victor Virgílio-da-Silva,
- Gerson S Profeta,
- Natália S Wassano,
- Luana Nunes Santos,
- Victor C Carregari,
- Artur HS Dias,
- Flavio P Veras,
- Lucas A Tavares,
- Julia Forato,
- Icaro MS Castro,
- Lícia C Silva-Costa,
- André C Palma,
- Eli Mansour,
- Raisa G Ulaf,
- Ana F Bernardes,
- Thyago A Nunes,
- Luciana C Ribeiro,
- Marcus V Agrela,
- Maria Luiza Moretti,
- Lucas I Buscaratti,
- Fernanda Crunfli,
- Raissa G Ludwig,
- Jaqueline A Gerhardt,
- Natália Munhoz-Alves,
- Ana Maria Marques,
- Renata Sesti-Costa,
- Mariene R Amorim,
- Daniel A Toledo-Teixeira,
- Pierina Lorencini Parise,
- Matheus Cavalheiro Martini,
- Karina Bispos-dos-Santos,
- Camila L Simeoni,
- Fabiana Granja,
- Virgínia C Silvestrini,
- Eduardo B de Oliveira,
- Vitor M Faca,
- Murilo Carvalho,
- Bianca G Castelucci,
- Alexandre B Pereira,
- Laís D Coimbra,
- Marieli MG Dias,
- Patricia B Rodrigues,
- Arilson Bernardo SP Gomes,
- Fabricio B Pereira,
- Leonilda MB Santos,
- Louis-Marie Bloyet,
- Spencer Stumpf,
- Marjorie C Pontelli,
- Sean Whelan,
- Andrei C Sposito,
- Robson F Carvalho,
- André S Vieira,
- Marco AR Vinolo,
- André Damasio,
- Licio Velloso,
- Ana Carolina M Figueira,
- Luis LP da Silva,
- Thiago Mattar Cunha,
- Helder I Nakaya,
- Henrique Marques-Souza,
- Rafael E Marques,
- Daniel Martins-de-Souza,
- Munir S Skaf,
- Jose Luiz Proenca-Modena,
- Pedro MM Moraes-Vieira,
- Marcelo A Mori,
- Alessandro S Farias
Affiliations
- Natalia S Brunetti
- ORCiD
- Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Gustavo G Davanzo
- Laboratory of Immunometabolism, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Diogo de Moraes
- Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Department of Structural and Functional Biology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, Brazil
- Allan JR Ferrari
- ORCiD
- Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas (UNICAMP), Campinas, Brazil
- Gabriela F Souza
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Stéfanie Primon Muraro
- ORCiD
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Thiago L Knittel
- Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Vinicius O Boldrini
- Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Lauar B Monteiro
- Laboratory of Immunometabolism, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- João Victor Virgílio-da-Silva
- Laboratory of Immunometabolism, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Gerson S Profeta
- Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Natália S Wassano
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Luana Nunes Santos
- ORCiD
- Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Victor C Carregari
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Artur HS Dias
- Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas (UNICAMP), Campinas, Brazil
- Flavio P Veras
- Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of BioMolecular Sciences, School of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto,, São Paulo, Brazil
- Lucas A Tavares
- ORCiD
- Department of Cell and Molecular Biology, Center for Virology Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Julia Forato
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Icaro MS Castro
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Lícia C Silva-Costa
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- André C Palma
- Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- Eli Mansour
- ORCiD
- Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- Raisa G Ulaf
- Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- Ana F Bernardes
- Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- Thyago A Nunes
- ORCiD
- Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- Luciana C Ribeiro
- Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- Marcus V Agrela
- Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- Maria Luiza Moretti
- Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- Lucas I Buscaratti
- Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Fernanda Crunfli
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Raissa G Ludwig
- Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Jaqueline A Gerhardt
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Natália Munhoz-Alves
- ORCiD
- Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Ana Maria Marques
- Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Renata Sesti-Costa
- Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
- Mariene R Amorim
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Daniel A Toledo-Teixeira
- ORCiD
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Pierina Lorencini Parise
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Matheus Cavalheiro Martini
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Karina Bispos-dos-Santos
- ORCiD
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Camila L Simeoni
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Fabiana Granja
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Virgínia C Silvestrini
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Eduardo B de Oliveira
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Vitor M Faca
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Murilo Carvalho
- National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil; Brazilian Synchrotron Light Laboratory (LNLS), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
- Bianca G Castelucci
- National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil; Brazilian Synchrotron Light Laboratory (LNLS), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
- Alexandre B Pereira
- National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
- Laís D Coimbra
- National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
- Marieli MG Dias
- ORCiD
- National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
- Patricia B Rodrigues
- Laboratory of Immunoinflammation, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil;, Campinas, Brazil
- Arilson Bernardo SP Gomes
- Laboratory of Immunoinflammation, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil;, Campinas, Brazil
- Fabricio B Pereira
- Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
- Leonilda MB Santos
- Neuroimmunology Unit, Department of Genetics, Microbiology and Immunology, University of Campinas (UNICAMP), Campinas, Brazil; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM) – Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Louis-Marie Bloyet
- ORCiD
- Washington University in St Louis, Department of Molecular Microbiology, St. Louis, United States
- Spencer Stumpf
- Washington University in St Louis, Department of Molecular Microbiology, St. Louis, United States
- Marjorie C Pontelli
- Washington University in St Louis, Department of Molecular Microbiology, St. Louis, United States
- Sean Whelan
- Washington University in St Louis, Department of Molecular Microbiology, St. Louis, United States
- Andrei C Sposito
- Laboratory of Vascular Biology and Arteriosclerosis, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- Robson F Carvalho
- ORCiD
- Department of Structural and Functional Biology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, Brazil
- André S Vieira
- Laboratory of Electrophysiology, Neurobiology and Behavior, University of Campinas (UNICAMP), Campinas, Brazil
- Marco AR Vinolo
- Laboratory of Immunoinflammation, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil;, Campinas, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil; Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil
- André Damasio
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil
- Licio Velloso
- Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil; Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil
- Ana Carolina M Figueira
- National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
- Luis LP da Silva
- ORCiD
- Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
- Thiago Mattar Cunha
- ORCiD
- Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto,, São Paulo, Brazil
- Helder I Nakaya
- ORCiD
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Henrique Marques-Souza
- ORCiD
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Rafael E Marques
- National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
- Daniel Martins-de-Souza
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil; D'Or Institute for Research and Education (IDOR), São Paulo, Brazil; National Institute of Science and Technology in Biomarkers for Neuropsychiatry (INCTINBION), São Paulo, Brazil
- Munir S Skaf
- Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas (UNICAMP), Campinas, Brazil
- Jose Luiz Proenca-Modena
- ORCiD
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil
- Pedro MM Moraes-Vieira
- Laboratory of Immunometabolism, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil; Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil
- Marcelo A Mori
- Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil; Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil
- Alessandro S Farias
- ORCiD
- Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Washington University in St Louis, Department of Molecular Microbiology, St. Louis, United States; Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil; Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, Brazil
- DOI
- https://doi.org/10.7554/eLife.84790
- Journal volume & issue
-
Vol. 12
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.
Keywords
