Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.
Laboratory of Immunometabolism, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.
Elife. 2023 Jul 31;12:e84790. 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 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.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是一种主要的全球呼吸道疾病爆发的病原体，称为 2019 年冠状病毒病（COVID-19）。SARS-CoV-2 主要感染肺部，并可能导致几种与疾病严重程度相关的免疫相关并发症，如淋巴细胞减少症和细胞因子风暴，并可预测死亡率。SARS-CoV-2 感染如何导致免疫系统功能障碍的机制尚不完全清楚。在这里，我们表明 SARS-CoV-2 感染人类辅助性 T 细胞（CD4 T 细胞），但不感染细胞毒性 T 细胞（CD8 T 细胞），并且存在于严重 COVID-19 患者的血液和支气管肺泡灌洗液中的辅助性 T 细胞中。我们证明了 SARS-CoV-2 刺突糖蛋白（S）直接结合 CD4 分子，进而介导 SARS-CoV-2 进入辅助性 T 细胞。这导致 CD4 T 细胞功能受损，并可能导致细胞死亡。感染 SARS-CoV-2 的辅助性 T 细胞表达更高水平的白细胞介素 10（IL-10），这与病毒持续存在和疾病严重程度相关。因此，CD4 介导的 SARS-CoV-2 对辅助性 T 细胞的感染可能导致 COVID-19 患者的免疫反应不佳。
