A prominent clinical symptom of 2019-novel coronavirus (nCoV) infection is hyposmia/anosmia (decrease or loss of sense of smell), along with general symptoms such as fatigue, shortness of breath, fever and cough. The identity of the cell lineages that underpin the infection-associated loss of olfaction could be critical for the clinical management of 2019-nCoV-infected individuals. Recent research has confirmed the role of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key host-specific cellular moieties responsible for the cellular entry of the virus. Accordingly, the ongoing medical examinations and the autopsy reports of the deceased individuals indicate that organs/tissues with high expression levels of ACE2, TMPRSS2 and other putative viral entry-associated genes are most vulnerable to the infection. We studied if anosmia in 2019-nCoV-infected individuals can be explained by the expression patterns associated with these host-specific moieties across the known olfactory epithelial cell types, identified from a recently published single-cell expression study. Our findings underscore selective expression of these viral entry-associated genes in a subset of sustentacular cells (SUSs), Bowman’s gland cells (BGCs) and stem cells of the olfactory epithelium. Co-expression analysis of ACE2 and TMPRSS2 and protein–protein interaction among the host and viral proteins elected regulatory cytoskeleton protein-enriched SUSs as the most vulnerable cell type of the olfactory epithelium. Furthermore, expression, structural and docking analyses of ACE2 revealed the potential risk of olfactory dysfunction in four additional mammalian species, revealing an evolutionarily conserved infection susceptibility. In summary, our findings provide a plausible cellular basis for the loss of smell in 2019-nCoV-infected patients.

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2019-nCoV 感染者嗅觉丧失的细胞基础

2019新型冠状病毒（nCoV）感染的一个突出临床症状是嗅觉减退/嗅觉缺失（嗅觉减退或丧失），以及疲劳、气短、发烧和咳嗽等一般症状。导致感染相关嗅觉丧失的细胞谱系的鉴定对于 2019-nCoV 感染者的临床管理可能至关重要。最近的研究证实了血管紧张素转换酶 2 (ACE2) 和跨膜蛋白酶丝氨酸 2 (TMPRSS2) 作为负责病毒进入细胞的关键宿主特异性细胞部分的作用。因此，正在进行的医学检查和死者尸检报告表明，ACE2、TMPRSS2和其他假定的病毒进入相关基因高表达水平的器官/组织最容易受到感染。我们研究了 2019-nCoV 感染者的嗅觉丧失是否可以通过与已知嗅觉上皮细胞类型中的这些宿主特异性部分相关的表达模式来解释，这些表达模式是从最近发表的单细胞表达研究中确定的。我们的研究结果强调了这些病毒进入相关基因在支持细胞（SUS）、鲍曼腺细胞（BGC）和嗅上皮干细胞的子集中的选择性表达。ACE2和TMPRSS2的共表达分析以及宿主和病毒蛋白之间的蛋白-蛋白相互作用选择富含调节性细胞骨架蛋白的 SUSs 作为嗅觉上皮最脆弱的细胞类型。此外，ACE2的表达、结构和对接分析揭示了另外四种哺乳动物物种嗅觉功能障碍的潜在风险，揭示了进化上保守的感染易感性。总之，我们的研究结果为 2019-nCoV 感染患者嗅觉丧失提供了合理的细胞基础。