Comparative Study of SARS-CoV-2, SARS-CoV-1, MERS-CoV, HCoV-229E and Influenza Host Gene Expression in Asthma: Importance of Sex, Disease Severity, and Epithelial Heterogeneity.
Comparative Study of SARS-CoV-2, SARS-CoV-1, MERS-CoV, HCoV-229E and Influenza Host Gene Expression in Asthma: Importance of Sex, Disease Severity, and Epithelial Heterogeneity.
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DOI：
10.3390/v13061081
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发表时间：
2021-06-05
期刊：
影响因子：
--
通讯作者：
Berdnikovs S
中科院分区：
文献类型：
--
作者：
Coden ME;Loffredo LF;Abdala-Valencia H;Berdnikovs S
慢性哮喘对SARS-CoV-2（COVID-19）和其他病毒感染的不同易感性的上皮特征目前尚不清楚。通过回顾Th 2低与Th 2高哮喘患者以及轻度、中度和重度哮喘患者的转录组学数据，我们描述了人类冠状病毒和流感病毒进入基因表达与性别、气道位置和疾病内型相关的变化。我们发现SARS-CoV-2相关基因ACE 2、TMPRSS 2、TMPRSS 4和SLC 6A 19的表达存在性二态性。ACE 2受体下调发生在女性中的Th 2高哮喘，而蛋白酶广泛协助冠状病毒和流感病毒的进入，TMPRSS 2，和TMPRSS 4，在两种性别的高度上调。总的来说，SARS-CoV-2相关基因表达的变化是特异性的哮喘的Th 2高分子内型，并根据哮喘的严重程度和气道位置而不同。ACE 2（COVID-19，SARS）和ANPEP（HCoV-229 E）病毒受体的下调与Th 2高哮喘中棒状细胞和纤毛细胞的丢失相关。同时，DPP 4（MERS-CoV）、ST 3GAL 4和ST 6 GAL 1（流感）的增加与杯状和基底活化细胞的增加相关。总的来说，这项研究阐明了性别，气道位置，疾病内型和上皮异质性的变化作为哮喘易感性的潜在因素，或缺乏SARS-CoV-2。
Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate, and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location, and disease endotype. We found sexual dimorphism in the expression of SARS-CoV-2-related genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2, and TMPRSS4, were highly upregulated in both sexes. Overall, changes in SARS-CoV-2-related gene expression were specific to the Th2 high molecular endotype of asthma and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors wascorrelated with loss of club and ciliated cells in Th2 high asthma. Meanwhile, the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) was associated with increased goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype, and changes in epithelial heterogeneity as potential factors underlying asthmatic susceptibility, or lack thereof, to SARS-CoV-2.
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影响因子：
6.7
作者：
Hatesuer B;Bertram S;Mehnert N;Bahgat MM;Nelson PS;Pöhlmann S;Schughart K
通讯作者：
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DOI：
10.1016/j.jaci.2017.04.010
发表时间：
2017-06
期刊：
The Journal of allergy and clinical immunology
影响因子：
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通讯作者：
Berdnikovs S
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10.1164/rccm.202003-0821oc
发表时间：
2020-07-01
影响因子：
24.7
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10.1164/rccm.202003-0541oc
发表时间：
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影响因子：
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作者：
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