Expression of the SARS-CoV-2 Entry Proteins, ACE2 and TMPRSS2, in Cells of the Olfactory Epithelium: Identification of Cell Types and Trends with Age

Expression of the SARS-CoV-2 Entry Proteins, ACE2 and TMPRSS2, in Cells of the Olfactory Epithelium: Identification of Cell Types and Trends with Age
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DOI:
10.1021/acschemneuro.0c00210
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发表时间:
2020-06-03
影响因子:
5
通讯作者:
Butowt, Rafal
Butowt, Rafal
中科院分区:
医学3区
文献类型:
--
作者:
Bilinska, Katarzyna;Jakubowska, Patrycja;Butowt, Rafal

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COVID-19大流行显示,许多患者(包括感染但无症状的患者)嗅觉丧失。嗅觉症状的潜在机制尚不清楚。使用小鼠模型,我们通过使用RNAseq、RT-PCR、原位杂交、Western印迹和免疫细胞化学来确定嗅上皮细胞是否表达SARS-CoV-2病毒进入的专性受体。我们发现,细胞表面蛋白ACE 2和蛋白酶TMPRSS 2的表达在嗅上皮的支持细胞,但没有,或少得多,在大多数嗅觉受体神经元。这些数据表明,支持细胞参与了SARS-CoV-2病毒的进入和COVID-19患者嗅觉的损害。我们还表明,表达的入口蛋白增加动物的老年。这可能解释了为什么老年人更容易感染SARS-CoV-2,如果在人类中也是如此。
The COVID-19 pandemic revealed that there is a loss of smell in many patients, including in infected but otherwise asymptomatic individuals. The underlying mechanisms for the olfactory symptoms are unclear. Using a mouse model, we determined whether cells in the olfactory epithelium express the obligatory receptors for entry of the SARS-CoV-2 virus by using RNAseq, RT-PCR, in situ hybridization, Western blot, and immunocytochemistry. We show that the cell surface protein ACE2 and the protease TMPRSS2 are expressed in sustentacular cells of the olfactory epithelium but not, or much less, in most olfactory receptor neurons. These data suggest that sustentacular cells are involved in SARS-CoV-2 virus entry and impairment of the sense of smell in COVID-19 patients. We also show that expression of the entry proteins increases in animals of old age. This may explain, if true also in humans, why individuals of older age are more susceptible to the SARS-CoV-2 infection.