SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients.

SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients.
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DOI:
10.1093/jmcb/mjac021
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发表时间:
2022-08-17
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学1区
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严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染与高炎症状态和淋巴细胞减少有关,这是疾病严重程度结果的特征和预后的标志。尽管细胞因子风暴和持续的炎症状态通常与免疫细胞耗竭有关,但目前尚不清楚免疫细胞的直接 SARS-CoV-2 感染是否也可以通过隐藏病毒复制在这种情况下发挥作用。我们发现单核细胞以及 B 和 T 淋巴细胞在体外容易受到 SARS-CoV-2 感染,积累与病毒 RNA 复制一致的双链 RNA,最终导致表达性 T 细胞凋亡。此外,流式细胞术和免疫荧光分析显示,2019 年冠状病毒病 (COVID-19) 患者的单核细胞和 B 淋巴细胞中经常检测到 SARS-CoV-2。自症状出现后,COVID-19 患者外周血单核细胞中 SARS-CoV-2 感染的单核细胞比例随着时间的推移而增加,死后肺组织中也检测到 SARS-CoV-2 阳性单核细胞、B 细胞和 CD4+ T 淋巴细胞。这些结果表明,COVID-19 患者血液循环白细胞的 SARS-CoV-2 感染可能对疾病的发病机制和进展、免疫功能障碍以及病毒在宿主体内的传播产生重要影响。
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that appears as both signature and prognosis of disease severity outcome. Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication. We found that monocytes, as well as both B and T lymphocytes, were susceptible to SARS-CoV-2 infection in vitro, accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis. In addition, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019 (COVID-19) patients. The rates of SARS-CoV-2-infected monocytes in peripheral blood mononuclear cells from COVID-19 patients increased over time from symptom onset, with SARS-CoV-2-positive monocytes, B cells, and CD4+ T lymphocytes also detected in postmortem lung tissue. These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in COVID-19 patients might have important implications for disease pathogenesis and progression, immune dysfunction, and virus spread within the host.
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