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

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Brunetti, Natalia S. ; Davanzo, Gustavo G. ; de Moraes, Diogo ; Ferrari, Allan J. R. ; Souza, Gabriela F. ; Muraro, Stefanie Primon ; Knittel, Thiago L. ; Boldrini, Vinicius O. ; Monteiro, Lauar B. ; Virgilio-da-Silva, Joo Victor ; Profeta, Gerson S. ; Wassano, Natalia S. ; Santos, Luana Nunes ; Carregari, Victor C. ; Dias, Artur H. S. ; Veras, Flavio P. ; Tavares, Lucas A. ; Forato, Julia ; Castro, Icaro M. S. ; Silva-Costa, Licia C. ; Palma, Andre C. ; Mansour, Eli ; Ulaf, Raisa G. ; Bernardes, Ana F. ; Nunes, Thyago A. ; Ribeiro, Luciana C. ; Agrela, Marcus V. ; Moretti, Maria Luiza ; Buscaratti, Lucas I. ; Crunfli, Fernanda ; Ludwig, Raissa G. ; Gerhardt, Jaqueline A. ; Munhoz-Alves, Natalia ; Marques, Ana Maria ; Sesti-Costa, Renata ; Amorim, Mariene R. ; Toledo-Teixeira, Daniel A. ; Parise, Pierina Lorencini ; Martini, Matheus Cavalheiro ; Bispos-dos-Santos, Karina ; Simeoni, Camila L. ; Granja, Fabiana ; Silvestrini, Virginia C. ; de Oliveira, Eduardo B. ; Faca, Vitor M. ; Carvalho, Murilo ; Castelucci, Bianca G. ; Pereira, Alexandre B. ; Coimbra, Lais D. ; Dias, Marieli M. G. ; Rodrigues, Patricia B. ; Gomes, Arilson Bernardo S. P. ; Pereira, Fabricio B. ; Santos, Leonilda M. B. ; Bloyet, Louis-Marie ; Stumpf, Spencer ; Pontelli, Marjorie C. ; Whelan, Sean ; Sposito, Andrei C. ; Carvalho, Robson F. ; Vieira, Andre S. ; Vinolo, Marco A. R. ; Damasio, Andre ; Velloso, Licio ; Figueira, Ana Carolina M. ; da Silva, Luis L. P. ; Cunha, Thiago Mattar ; Nakaya, Helder I. ; Marques-Souza, Henrique ; Marques, Rafael E. ; Martins-de-Souza, Daniel ; Skaf, Munir S. ; Proenca-Modena, Jose Luiz ; Moraes-Vieira, Pedro M. M. ; Mori, Marcelo A. ; Farias, Alessandro S.

• Document type: Journal article
• Source: eLIFE; v. 12, p. 26-pg., 2023-07-31.

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. (AU)

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