1. SARS-CoV-2 uses CD4 to infect T helper lymphocytes.
- Author
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Brunetti NS, Davanzo GG, de Moraes D, Ferrari AJR, Souza GF, Muraro SP, Knittel TL, Boldrini VO, Monteiro LB, Virgílio-da-Silva JV, Profeta GS, Wassano NS, Nunes Santos L, Carregari VC, Dias AHS, Veras FP, Tavares LA, Forato J, Castro IMS, Silva-Costa LC, Palma AC, Mansour E, Ulaf RG, Bernardes AF, Nunes TA, Ribeiro LC, Agrela MV, Moretti ML, Buscaratti LI, Crunfli F, Ludwig RG, Gerhardt JA, Munhoz-Alves N, Marques AM, Sesti-Costa R, Amorim MR, Toledo-Teixeira DA, Parise PL, Martini MC, Bispos-Dos-Santos K, Simeoni CL, Granja F, Silvestrini VC, de Oliveira EB, Faca VM, Carvalho M, Castelucci BG, Pereira AB, Coimbra LD, Dias MMG, Rodrigues PB, Gomes ABSP, Pereira FB, Santos LMB, Bloyet LM, Stumpf S, Pontelli MC, Whelan S, Sposito AC, Carvalho RF, Vieira AS, Vinolo MAR, Damasio A, Velloso L, Figueira ACM, da Silva LLP, Cunha TM, Nakaya HI, Marques-Souza H, Marques RE, Martins-de-Souza D, Skaf MS, Proenca-Modena JL, Moraes-Vieira PMM, Mori MA, and Farias AS
- Subjects
- Humans, CD8-Positive T-Lymphocytes, T-Lymphocytes, Helper-Inducer, Lung, SARS-CoV-2, COVID-19
- 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., Competing Interests: NB, GD, Dd, AF, GS, SM, TK, VB, LM, JV, GP, NW, LN, VC, AD, FV, LT, JF, IC, LS, AP, EM, RU, AB, TN, LR, MA, MM, LB, FC, RL, JG, NM, AM, RS, MA, DT, PP, MM, KB, CS, FG, VS, Ed, VF, MC, BC, AP, LC, MD, PR, AG, FP, LS, LB, SS, MP, SW, AS, RC, AV, MV, AD, LV, AF, Ld, TC, HN, HM, RM, DM, MS, JP, PM, MM, AF No competing interests declared, (© 2023, Brunetti, Davanzo, de Moraes et al.)- Published
- 2023
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