Tissue factor expression, extracellular vesicles, and thrombosis after infection with the respiratory viruses influenza A virus and coronavirus.

Tissue factor expression, extracellular vesicles, and thrombosis after infection with the respiratory viruses influenza A virus and coronavirus.
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呼吸道病毒A型流感病毒和冠状病毒感染后的组织因子表达、细胞外囊泡和血栓形成。

DOI:
10.1111/jth.15509
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发表时间:
2021-11
影响因子:
10.4
通讯作者:
Antoniak, Silvio
Antoniak, Silvio
中科院分区:
医学2区
文献类型:
--
作者:
Mackman, Nigel;Grover, Steven P.;Antoniak, Silvio

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组织因子(TF)在病毒感染过程中在多种细胞中被诱导,可能导致弥漫性血管内凝血和血栓形成。表达转铁蛋白的细胞还将转铁蛋白阳性的细胞外小泡(EVS)释放到循环中,这可以通过EVTF活性测定来测量。本文综述了甲型流感病毒(IAV)、冠状病毒(CoV)、SARS冠状病毒(SARS-CoV-2)、中东呼吸综合征冠状病毒(MERS-CoV)感染后Tf表达、Tf阳性EV、凝血激活和血栓形成的研究进展。目前流行的2019年冠状病毒病(新冠肺炎)是由感染SARS-CoV-2引起的。感染IAV的小鼠肺上皮细胞TF表达增加,EVTF活性增加,支气管肺泡灌洗液中凝血功能激活。感染MERS-CoV、SARS-CoV和SARS-CoV-2的小鼠肺组织转铁蛋白表达也增加。对重症新冠肺炎患者的肺泡灌洗液进行单细胞核糖核酸测序分析,发现肺泡灌洗液上皮细胞TFm RNA表达增加。在感染SARS冠状病毒的外周血单核细胞中可观察到TF的表达。新冠肺炎患者外周血单核细胞、血小板-单核细胞聚合体中的单核细胞和中性粒细胞也表达TF。重度IAV和新冠肺炎患者循环血管紧张素转换因子活性升高。重要的是,血管紧张素转换因子活性与重症IAV患者的死亡率以及新冠肺炎患者的血浆D-二聚体、严重程度、血栓形成和死亡率相关。这些研究强烈表明,感染IAV和病原性CoV的患者中TF表达增加导致血栓形成。
Tissue factor (TF) is induced in a variety of cell types during viral infection, which likely contributes to disseminated intravascular coagulation and thrombosis. TF‐expressing cells also release TF‐positive extracellular vesicles (EVs) into the circulation that can be measured using an EVTF activity assay. This review summarizes studies that analyze TF expression, TF‐positive EVs, activation of coagulation, and thrombosis after infection with influenza A virus (IAV) and coronaviruses (CoVs), including severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), SARS‐CoV, and Middle East respiratory syndrome CoV (MERS‐CoV). The current pandemic of coronavirus disease 2019 (COVID‐19) is caused by infection with SARS‐CoV‐2. Infection of mice with IAV increased TF expression in lung epithelial cells as well as increased EVTF activity and activation of coagulation in the bronchoalveolar lavage fluid (BALF). Infection of mice with MERS‐CoV, SARS‐CoV, and SARS‐CoV‐2 also increased lung TF expression. Single‐cell RNA sequencing analysis on the BALF from severe COVID‐19 patients revealed increased TF mRNA expression in epithelial cells. TF expression was observed in peripheral blood mononuclear cells infected with SARS‐CoV. TF was also expressed by peripheral blood mononuclear cells, monocytes in platelet‐monocyte aggregates, and neutrophils isolated from COVID‐19 patients. Elevated circulating EVTF activity was observed in severe IAV and COVID‐19 patients. Importantly, EVTF activity was associated with mortality in severe IAV patients and with plasma D‐dimer, severity, thrombosis, and mortality in COVID‐19 patients. These studies strongly suggest that increased TF expression in patients infected with IAV and pathogenic CoVs contributes to thrombosis.
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发表时间: 2021-05
影响因子: 4.6
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DOI: 10.1172/jci137244
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