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

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-CostaAndré 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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Article numbere84790
JournaleLife
Volume12
DOIs
StatePublished - 2023

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