Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia.
Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia.
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DOI：
10.1126/sciadv.abc5801
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发表时间：
2020-07-31
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
嗅觉功能改变是COVID-19的常见症状，但其病因尚不清楚。一个关键的问题是SARS-CoV-2（CoV-2）-COVID-19的致病因子-是否通过感染嗅球中的嗅觉感觉神经元或其靶点直接影响嗅觉，或者通过干扰支持细胞间接影响嗅觉。在这里，我们确定细胞类型的嗅上皮和嗅球表达SARS-CoV-2细胞进入分子。批量测序表明，小鼠，非人灵长类动物和人类嗅觉粘膜表达两个关键基因参与CoV-2的进入，ACE 2和TMPRSS 2。然而，单细胞测序显示ACE 2在支持细胞、干细胞和血管周围细胞中表达，而不是在神经元中表达。免疫染色证实了这些结果，并揭示了ACE 2蛋白在小鼠背侧嗅上皮支持细胞和嗅球周细胞中的普遍表达。这些发现表明，非神经元细胞类型的CoV-2感染导致COVID-19患者嗅觉丧失和相关的气味感知障碍。
Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.
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