SARS-CoV-2 uses CD4 to infect T helper lymphocytes-Reference-Cited by-同舟云学术

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

Published:2023-07-31 Issue: Volume:12 Page:
ISSN:2050-084X
Container-title:eLife
language:en
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Author:

Brunetti Natalia S¹^ORCID,Davanzo Gustavo G²,de Moraes Diogo³⁴,Ferrari Allan JR⁵^ORCID,Souza Gabriela F⁶,Muraro Stéfanie Primon⁶^ORCID,Knittel Thiago L³,Boldrini Vinicius O¹,Monteiro Lauar B²,Virgílio-da-Silva João Victor²,Profeta Gerson S³,Wassano Natália S⁷,Nunes Santos Luana⁸^ORCID,Carregari Victor C⁹,Dias Artur HS⁵,Veras Flavio P¹⁰¹¹¹²,Tavares Lucas A¹³^ORCID,Forato Julia⁶,Castro Icaro MS¹⁴,Silva-Costa Lícia C⁹,Palma André C¹⁵,Mansour Eli¹⁵^ORCID,Ulaf Raisa G¹⁵,Bernardes Ana F¹⁵,Nunes Thyago A¹⁵^ORCID,Ribeiro Luciana C¹⁵,Agrela Marcus V¹⁵,Moretti Maria Luiza¹⁵,Buscaratti Lucas I⁸,Crunfli Fernanda⁹,Ludwig Raissa G³,Gerhardt Jaqueline A⁷,Munhoz-Alves Natália¹^ORCID,Marques Ana Maria¹,Sesti-Costa Renata¹¹⁶,Amorim Mariene R⁶,Toledo-Teixeira Daniel A⁶^ORCID,Parise Pierina Lorencini⁶,Martini Matheus Cavalheiro⁶,Bispos-dos-Santos Karina⁶^ORCID,Simeoni Camila L⁶,Granja Fabiana⁶,Silvestrini Virgínia C¹⁷,de Oliveira Eduardo B¹⁷,Faca Vitor M¹⁷,Carvalho Murilo¹⁸¹⁹,Castelucci Bianca G¹⁸¹⁹,Pereira Alexandre B¹⁸,Coimbra Laís D¹⁸,Dias Marieli MG¹⁸^ORCID,Rodrigues Patricia B²⁰,Gomes Arilson Bernardo SP²⁰,Pereira Fabricio B¹⁶,Santos Leonilda MB²¹²²,Bloyet Louis-Marie²³^ORCID,Stumpf Spencer²³,Pontelli Marjorie C²³,Whelan Sean²³,Sposito Andrei C²⁴,Carvalho Robson F⁴^ORCID,Vieira André S²⁵,Vinolo Marco AR²⁰²⁶²⁷,Damasio André⁷²⁶,Velloso Licio¹⁵²⁷,Figueira Ana Carolina M¹⁸,da Silva Luis LP¹⁰^ORCID,Cunha Thiago Mattar¹⁰¹²^ORCID,Nakaya Helder I¹⁴^ORCID,Marques-Souza Henrique⁷⁸^ORCID,Marques Rafael E¹⁸,Martins-de-Souza Daniel⁹²⁶²⁸²⁹,Skaf Munir S⁵,Proenca-Modena Jose Luiz⁶²⁶^ORCID,Moraes-Vieira Pedro MM²²⁶²⁷,Mori Marcelo A³²⁶²⁷,Farias Alessandro S¹²³²⁶²⁷^ORCID

Affiliation:

1. Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP)

2. Laboratory of Immunometabolism, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP)

3. Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP)

4. Department of Structural and Functional Biology, Institute of Biosciences, Sao Paulo State University (UNESP)

5. Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas (UNICAMP)

6. Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP)

7. Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP)

8. Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP)

9. Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP)

10. Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto

11. Department of BioMolecular Sciences, School of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto

12. Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto,

13. Department of Cell and Molecular Biology, Center for Virology Research, Ribeirão Preto Medical School, University of São Paulo

14. Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo

15. Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP)

16. Hematology and Hemotherapy Center, University of Campinas (UNICAMP)

17. Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo

18. National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM)

19. Brazilian Synchrotron Light Laboratory (LNLS), Brazilian Center for Research in Energy and Materials (CNPEM)

20. Laboratory of Immunoinflammation, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil;

21. Neuroimmunology Unit, Department of Genetics, Microbiology and Immunology, University of Campinas (UNICAMP)

22. National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM) – Oswaldo Cruz Institute, Oswaldo Cruz Foundation

23. Washington University in St Louis, Department of Molecular Microbiology

24. Laboratory of Vascular Biology and Arteriosclerosis, School of Medical Sciences, University of Campinas (UNICAMP)

25. Laboratory of Electrophysiology, Neurobiology and Behavior, University of Campinas (UNICAMP)

26. Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP)

27. Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP)

28. D'Or Institute for Research and Education (IDOR)

29. National Institute of Science and Technology in Biomarkers for Neuropsychiatry (INCTINBION)

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.

Funder

Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas

Fundação de Amparo à Pesquisa do Estado de São Paulo

Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação

Financiadora de Estudos e Projetos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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