tetano
Editor, Senior Moderator
Elife
. 2023 Jul 31;12:e84790.
doi: 10.7554/eLife.84790. SARS-CoV-2 uses CD4 to infect T helper lymphocytes
Natalia S Brunetti[SUP] #[/SUP][SUP] 1 [/SUP], Gustavo G Davanzo[SUP] #[/SUP][SUP] 2 [/SUP], Diogo de Moraes[SUP] #[/SUP][SUP] 3 4 [/SUP], Allan J R Ferrari[SUP] #[/SUP][SUP] 5 [/SUP], Gabriela F Souza[SUP] #[/SUP][SUP] 6 [/SUP], Stéfanie Primon Muraro[SUP] #[/SUP][SUP] 6 [/SUP], Thiago L Knittel[SUP] #[/SUP][SUP] 3 [/SUP], Vinicius O Boldrini[SUP] #[/SUP][SUP] 1 [/SUP], Lauar B Monteiro[SUP] #[/SUP][SUP] 2 [/SUP], João Victor Virgílio-da-Silva[SUP] #[/SUP][SUP] 2 [/SUP], Gerson S Profeta[SUP] #[/SUP][SUP] 3 [/SUP], Natália S Wassano[SUP] #[/SUP][SUP] 7 [/SUP], Luana Nunes Santos[SUP] #[/SUP][SUP] 8 [/SUP], Victor C Carregari[SUP] #[/SUP][SUP] 9 [/SUP], Artur H S Dias[SUP] #[/SUP][SUP] 5 [/SUP], Flavio P Veras[SUP] 10 11 12 [/SUP], Lucas A Tavares[SUP] 13 [/SUP], Julia Forato[SUP] 6 [/SUP], Icaro M S Castro[SUP] 14 [/SUP], Lícia C Silva-Costa[SUP] 9 [/SUP], André C Palma[SUP] 15 [/SUP], Eli Mansour[SUP] 15 [/SUP], Raisa G Ulaf[SUP] 15 [/SUP], Ana F Bernardes[SUP] 15 [/SUP], Thyago A Nunes[SUP] 15 [/SUP], Luciana C Ribeiro[SUP] 15 [/SUP], Marcus V Agrela[SUP] 15 [/SUP], Maria Luiza Moretti[SUP] 15 [/SUP], Lucas I Buscaratti[SUP] 8 [/SUP], Fernanda Crunfli[SUP] 9 [/SUP], Raissa G Ludwig[SUP] 3 [/SUP], Jaqueline A Gerhardt[SUP] 7 [/SUP], Natália Munhoz-Alves[SUP] 1 [/SUP], Ana Maria Marques[SUP] 1 [/SUP], Renata Sesti-Costa[SUP] 1 16 [/SUP], Mariene R Amorim[SUP] 6 [/SUP], Daniel A Toledo-Teixeira[SUP] 6 [/SUP], Pierina Lorencini Parise[SUP] 6 [/SUP], Matheus Cavalheiro Martini[SUP] 6 [/SUP], Karina Bispos-Dos-Santos[SUP] 6 [/SUP], Camila L Simeoni[SUP] 6 [/SUP], Fabiana Granja[SUP] 6 [/SUP], Virgínia C Silvestrini[SUP] 17 [/SUP], Eduardo B de Oliveira[SUP] 17 [/SUP], Vitor M Faca[SUP] 17 [/SUP], Murilo Carvalho[SUP] 18 19 [/SUP], Bianca G Castelucci[SUP] 18 19 [/SUP], Alexandre B Pereira[SUP] 18 [/SUP], Laís D Coimbra[SUP] 18 [/SUP], Marieli M G Dias[SUP] 18 [/SUP], Patricia B Rodrigues[SUP] 20 [/SUP], Arilson Bernardo S P Gomes[SUP] 20 [/SUP], Fabricio B Pereira[SUP] 16 [/SUP], Leonilda M B Santos[SUP] 21 22 [/SUP], Louis-Marie Bloyet[SUP] 23 [/SUP], Spencer Stumpf[SUP] 23 [/SUP], Marjorie C Pontelli[SUP] 23 [/SUP], Sean Whelan[SUP] 23 [/SUP], Andrei C Sposito[SUP] 24 [/SUP], Robson F Carvalho[SUP] 4 [/SUP], André S Vieira[SUP] 25 [/SUP], Marco A R Vinolo[SUP] 20 26 27 [/SUP], André Damasio[SUP] 7 26 [/SUP], Licio Velloso[SUP] 15 27 [/SUP], Ana Carolina M Figueira[SUP] 18 [/SUP], Luis L P da Silva[SUP] 10 [/SUP], Thiago Mattar Cunha[SUP] 10 12 [/SUP], Helder I Nakaya[SUP] 14 [/SUP], Henrique Marques-Souza[SUP] 7 8 [/SUP], Rafael E Marques[SUP] 18 [/SUP], Daniel Martins-de-Souza[SUP] 9 26 28 29 [/SUP], Munir S Skaf[SUP] 5 [/SUP], Jose Luiz Proenca-Modena[SUP] 6 26 [/SUP], Pedro M M Moraes-Vieira[SUP] 2 26 27 [/SUP], Marcelo A Mori[SUP] 3 26 27 [/SUP], Alessandro S Farias[SUP] 1 23 26 27 [/SUP]
Affiliations
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[SUP]+[/SUP] T helper cells, but not CD8[SUP]+[/SUP] 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.
Keywords: COVID-19; T cells; human; immunology; inflammation; virus infection.
. 2023 Jul 31;12:e84790.
doi: 10.7554/eLife.84790. SARS-CoV-2 uses CD4 to infect T helper lymphocytes
Natalia S Brunetti[SUP] #[/SUP][SUP] 1 [/SUP], Gustavo G Davanzo[SUP] #[/SUP][SUP] 2 [/SUP], Diogo de Moraes[SUP] #[/SUP][SUP] 3 4 [/SUP], Allan J R Ferrari[SUP] #[/SUP][SUP] 5 [/SUP], Gabriela F Souza[SUP] #[/SUP][SUP] 6 [/SUP], Stéfanie Primon Muraro[SUP] #[/SUP][SUP] 6 [/SUP], Thiago L Knittel[SUP] #[/SUP][SUP] 3 [/SUP], Vinicius O Boldrini[SUP] #[/SUP][SUP] 1 [/SUP], Lauar B Monteiro[SUP] #[/SUP][SUP] 2 [/SUP], João Victor Virgílio-da-Silva[SUP] #[/SUP][SUP] 2 [/SUP], Gerson S Profeta[SUP] #[/SUP][SUP] 3 [/SUP], Natália S Wassano[SUP] #[/SUP][SUP] 7 [/SUP], Luana Nunes Santos[SUP] #[/SUP][SUP] 8 [/SUP], Victor C Carregari[SUP] #[/SUP][SUP] 9 [/SUP], Artur H S Dias[SUP] #[/SUP][SUP] 5 [/SUP], Flavio P Veras[SUP] 10 11 12 [/SUP], Lucas A Tavares[SUP] 13 [/SUP], Julia Forato[SUP] 6 [/SUP], Icaro M S Castro[SUP] 14 [/SUP], Lícia C Silva-Costa[SUP] 9 [/SUP], André C Palma[SUP] 15 [/SUP], Eli Mansour[SUP] 15 [/SUP], Raisa G Ulaf[SUP] 15 [/SUP], Ana F Bernardes[SUP] 15 [/SUP], Thyago A Nunes[SUP] 15 [/SUP], Luciana C Ribeiro[SUP] 15 [/SUP], Marcus V Agrela[SUP] 15 [/SUP], Maria Luiza Moretti[SUP] 15 [/SUP], Lucas I Buscaratti[SUP] 8 [/SUP], Fernanda Crunfli[SUP] 9 [/SUP], Raissa G Ludwig[SUP] 3 [/SUP], Jaqueline A Gerhardt[SUP] 7 [/SUP], Natália Munhoz-Alves[SUP] 1 [/SUP], Ana Maria Marques[SUP] 1 [/SUP], Renata Sesti-Costa[SUP] 1 16 [/SUP], Mariene R Amorim[SUP] 6 [/SUP], Daniel A Toledo-Teixeira[SUP] 6 [/SUP], Pierina Lorencini Parise[SUP] 6 [/SUP], Matheus Cavalheiro Martini[SUP] 6 [/SUP], Karina Bispos-Dos-Santos[SUP] 6 [/SUP], Camila L Simeoni[SUP] 6 [/SUP], Fabiana Granja[SUP] 6 [/SUP], Virgínia C Silvestrini[SUP] 17 [/SUP], Eduardo B de Oliveira[SUP] 17 [/SUP], Vitor M Faca[SUP] 17 [/SUP], Murilo Carvalho[SUP] 18 19 [/SUP], Bianca G Castelucci[SUP] 18 19 [/SUP], Alexandre B Pereira[SUP] 18 [/SUP], Laís D Coimbra[SUP] 18 [/SUP], Marieli M G Dias[SUP] 18 [/SUP], Patricia B Rodrigues[SUP] 20 [/SUP], Arilson Bernardo S P Gomes[SUP] 20 [/SUP], Fabricio B Pereira[SUP] 16 [/SUP], Leonilda M B Santos[SUP] 21 22 [/SUP], Louis-Marie Bloyet[SUP] 23 [/SUP], Spencer Stumpf[SUP] 23 [/SUP], Marjorie C Pontelli[SUP] 23 [/SUP], Sean Whelan[SUP] 23 [/SUP], Andrei C Sposito[SUP] 24 [/SUP], Robson F Carvalho[SUP] 4 [/SUP], André S Vieira[SUP] 25 [/SUP], Marco A R Vinolo[SUP] 20 26 27 [/SUP], André Damasio[SUP] 7 26 [/SUP], Licio Velloso[SUP] 15 27 [/SUP], Ana Carolina M Figueira[SUP] 18 [/SUP], Luis L P da Silva[SUP] 10 [/SUP], Thiago Mattar Cunha[SUP] 10 12 [/SUP], Helder I Nakaya[SUP] 14 [/SUP], Henrique Marques-Souza[SUP] 7 8 [/SUP], Rafael E Marques[SUP] 18 [/SUP], Daniel Martins-de-Souza[SUP] 9 26 28 29 [/SUP], Munir S Skaf[SUP] 5 [/SUP], Jose Luiz Proenca-Modena[SUP] 6 26 [/SUP], Pedro M M Moraes-Vieira[SUP] 2 26 27 [/SUP], Marcelo A Mori[SUP] 3 26 27 [/SUP], Alessandro S Farias[SUP] 1 23 26 27 [/SUP]
Affiliations
- PMID: 37523305
- DOI: 10.7554/eLife.84790
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[SUP]+[/SUP] T helper cells, but not CD8[SUP]+[/SUP] 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.
Keywords: COVID-19; T cells; human; immunology; inflammation; virus infection.