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

Autor: Brunetti NS; Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Davanzo GG; Laboratory of Immunometabolism, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., de Moraes D; 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., Ferrari AJR; Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas (UNICAMP), Campinas, Brazil., Souza GF; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Muraro SP; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Knittel TL; Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Boldrini VO; Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Monteiro LB; Laboratory of Immunometabolism, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Virgílio-da-Silva JV; Laboratory of Immunometabolism, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Profeta GS; Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Wassano NS; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Nunes Santos L; Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Carregari VC; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Dias AHS; Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas (UNICAMP), Campinas, Brazil., Veras FP; 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., Tavares LA; Department of Cell and Molecular Biology, Center for Virology Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Forato J; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Castro IMS; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Silva-Costa LC; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Palma AC; Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Mansour E; Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Ulaf RG; Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Bernardes AF; Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Nunes TA; Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Ribeiro LC; Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Agrela MV; Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Moretti ML; Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Buscaratti LI; Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Crunfli F; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Ludwig RG; Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Gerhardt JA; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Munhoz-Alves N; Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Marques AM; Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Sesti-Costa R; 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., Amorim MR; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Toledo-Teixeira DA; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Parise PL; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Martini MC; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Bispos-Dos-Santos K; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Simeoni CL; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Granja F; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Silvestrini VC; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., de Oliveira EB; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Faca VM; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Carvalho M; 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., Castelucci BG; 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., Pereira AB; National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Coimbra LD; National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Dias MMG; National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Rodrigues PB; Laboratory of Immunoinflammation, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil;, Campinas, Brazil., Gomes ABSP; Laboratory of Immunoinflammation, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil;, Campinas, Brazil., Pereira FB; Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil., Santos LMB; 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., Bloyet LM; Washington University in St Louis, Department of Molecular Microbiology, St. Louis, United States., Stumpf S; Washington University in St Louis, Department of Molecular Microbiology, St. Louis, United States., Pontelli MC; Washington University in St Louis, Department of Molecular Microbiology, St. Louis, United States., Whelan S; Washington University in St Louis, Department of Molecular Microbiology, St. Louis, United States., Sposito AC; Laboratory of Vascular Biology and Arteriosclerosis, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Carvalho RF; Department of Structural and Functional Biology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, Brazil., Vieira AS; Laboratory of Electrophysiology, Neurobiology and Behavior, University of Campinas (UNICAMP), Campinas, Brazil., Vinolo MAR; 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., Damasio A; 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., Velloso L; 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., Figueira ACM; National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., da Silva LLP; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Cunha TM; 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., Nakaya HI; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Marques-Souza H; 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., Marques RE; National Biosciences Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Martins-de-Souza D; 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., Skaf MS; Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas (UNICAMP), Campinas, Brazil., Proenca-Modena JL; 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., Moraes-Vieira PMM; 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., Mori MA; 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., Farias AS; 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.
Jazyk: angličtina
Zdroj: ELife [Elife] 2023 Jul 31; Vol. 12. Date of Electronic Publication: 2023 Jul 31.
DOI: 10.7554/eLife.84790
Abstrakt: 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.
Competing Interests: NB, GD, Dd, AF, GS, SM, TK, VB, LM, JV, GP, NW, LN, VC, AD, FV, LT, JF, IC, LS, AP, EM, RU, AB, TN, LR, MA, MM, LB, FC, RL, JG, NM, AM, RS, MA, DT, PP, MM, KB, CS, FG, VS, Ed, VF, MC, BC, AP, LC, MD, PR, AG, FP, LS, LB, SS, MP, SW, AS, RC, AV, MV, AD, LV, AF, Ld, TC, HN, HM, RM, DM, MS, JP, PM, MM, AF No competing interests declared
(© 2023, Brunetti, Davanzo, de Moraes et al.)
Databáze: MEDLINE