Cystic Fibrosis Center of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Section of Clinical Biochemistry, University of Verona, Verona, Italy.
Nat Commun. 2023 Jan 10;14(1):132. doi: 10.1038/s41467-023-35862-0.
As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis could be considered a comorbidity for coronavirus disease 2019. Instead, current clinical evidence seems to be heading in the opposite direction. To clarify whether host factors expressed by the Cystic Fibrosis epithelia may influence coronavirus disease 2019 progression, here we describe the expression of SARS-CoV-2 receptors in primary airway epithelial cells. We show that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral entry and replication in Cystic Fibrosis cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin 6 in healthy donor-derived primary airway epithelial cells, but a very weak response in primary Cystic Fibrosis cells. Collectively, these data support that Cystic Fibrosis condition may be at least partially protecting from SARS-CoV-2 infection.
作为一种以严重肺部疾病为特征的遗传性疾病，囊性纤维化可以被认为是 2019 年冠状病毒病的合并症。然而，目前的临床证据似乎指向相反的方向。为了阐明囊性纤维化上皮细胞表达的宿主因素是否可能影响 2019 年冠状病毒病的进展，我们在这里描述了 SARS-CoV-2 受体在原代气道上皮细胞中的表达。我们表明，血管紧张素转换酶 2（ACE2）的表达和定位受囊性纤维化跨膜电导调节因子（CFTR）通道调节。一致地，我们的结果表明，功能失调的 CFTR 通道改变了对 SARS-CoV-2 感染的易感性，导致囊性纤维化细胞中的病毒进入和复制减少。根据 ACE2 表达的模式，SARS-CoV-2 刺突（S）蛋白在健康供体来源的原代气道上皮细胞中诱导高水平的白细胞介素 6，但在原代囊性纤维化细胞中反应非常弱。总的来说，这些数据支持囊性纤维化的状况至少可能部分地保护免受 SARS-CoV-2 感染。
