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

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. © 2023, Brunetti, Davanzo, de Moraes et al.

Citation

Natalia S Brunetti, Gustavo G Davanzo, Diogo de Moraes, Allan J R 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 H S Dias, Flavio P Veras, Lucas A Tavares, Julia Forato, Icaro M S 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 M G Dias, Patricia B Rodrigues, Arilson Bernardo S P Gomes, Fabricio B Pereira, Leonilda M B Santos, Louis-Marie Bloyet, Spencer Stumpf, Marjorie C Pontelli, Sean Whelan, Andrei C Sposito, Robson F Carvalho, André S Vieira, Marco A R Vinolo, André Damasio, Licio Velloso, Ana Carolina M Figueira, Luis L P 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 M M Moraes-Vieira, Marcelo A Mori, Alessandro S Farias. SARS-CoV-2 uses CD4 to infect T helper lymphocytes. eLife. 2023 Jul 31;12

Mesh Tags

PMID: 37523305

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