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

2023; eLife Sciences Publications Ltd; Volume: 12; Linguagem: Inglês

10.7554/elife.84790

2050-084X

Natália S. Brunetti, Gustavo Gastão Davanzo, Diogo de Moraes, A. Ferrari, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, Thiago L. Knittel, Vinícius O. Boldrini, Lauar de Brito Monteiro, João Victor Virgílio-da-Silva, Gerson S. Profeta, Natália Sayuri Wassano, Luana Nunes Santos, Victor Corasolla Carregari, Artur HS Dias, Flávio P. Veras, Lucas Tavares, Julia Forato, Ícaro Maia Santos de Castro, Lícia C. Silva-Costa, André C. Palma, Eli Mansour, Raisa G. Ulaf, Ana Flávia Bernardes, Thyago A. Nunes, Luciana C. Ribeiro, Marcus V. Agrela, Maria Luíza Moretti, Lucas I Buscaratti, Fernanda Crunfli, Raissa G. Ludwig, Jaqueline Aline 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 Campos Silvestrini, Eduardo Basílio de Oliveira, Vítor M. Faça, Murilo de Carvalho, Bianca Gazieri Castelucci, Alexandre Borin, Laís D. Coimbra, Marieli M. G. Dias, Patrícia Brito Rodrigues, Arilson Bernardo SP Gomes, Fabrício Bíscaro Pereira, Leonilda MB Santos, Louis-Marie Bloyet, Spencer Stumpf, Marjorie Cornejo Pontelli, Sean P. J. Whelan, Andrei C. Spósito, Robson Francisco Carvalho, André Schwambach Vieira, Marco AR Vinolo, André Damásio, Lı́cio A. Velloso, Ana Carolina Migliorini Figueira, Luis LP da Silva, Thiago M. Cunha, Helder I. Nakaya, Henrique Marques‐Souza, Rafael Elias Marques, Daniel Martins‐de‐Souza, Munir S. Skaf, José Luiz Proença-Módena, Pedro M. Moraes‐Vieira, Marcelo A. Mori, Alessandro S. Farias,

Long-Term Effects of COVID-19

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.