Pagani Isabel, Venturini Arianna, Capurro Valeria, Nonis Alessandro, Ghezzi Silvia, Lena Mariateresa, Alcalá-Franco Beatriz, Gianferro Fabrizio, Guidone Daniela, Colombo Carla, Pedemonte Nicoletta, Bragonzi Alessandra, Cigana Cristina, Galietta Luis J V, Vicenzi Elisa
Viral Pathogenesis and Biosafety Unit and.
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Am J Respir Cell Mol Biol. 2025 Mar;72(3):308-319. doi: 10.1165/rcmb.2024-0213OC.
The coronavirus disease (COVID-19) pandemic has underscored the impact of viral infections on individuals with cystic fibrosis (CF). Initial observations suggested lower COVID-19 rates among CF populations; however, subsequent clinical data have presented a more complex scenario. This study aimed to investigate how bronchial epithelial cells from individuals with and without CF, including various (CF transmembrane conductance regulator) mutations, respond to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and SARS-CoV. Comparisons with the influenza A virus (IAV) were included based on evidence that patients with CF experience heightened morbidity from IAV infection. Our findings showed that CF epithelial cells exhibited reduced replication of SARS-CoV-2, regardless of the type of mutation or SARS-CoV-2 variant, as well as the original 2003 SARS-CoV. In contrast, these cells displayed more efficient IAV replication than non-CF cells. Interestingly, the reduced susceptibility to SARS-CoV-2 in CF was not linked to the expression of ACE2 (angiotensin-converting enzyme 2) receptor or to CFTR dysfunction, as pharmacological treatments to restore CFTR function did not normalize the viral response. Both SARS-CoV-2 infection and CFTR function influenced the concentrations of certain cytokines and chemokines, although these effects were not correlated. Overall, this study reveals a unique viral response in CF epithelial cells, characterized by reduced replication for some viruses like SARS-CoV-2, while showing increased susceptibility to others, such as IAV. This research offers a new perspective on CF and viral interactions, emphasizing the need for further investigation into the mechanisms underlying these differences.
冠状病毒病（COVID-19）大流行凸显了病毒感染对囊性纤维化（CF）患者的影响。最初的观察结果表明CF人群中COVID-19感染率较低；然而，随后的临床数据呈现出更为复杂的情况。本研究旨在调查有无CF的个体（包括各种CF跨膜传导调节因子（CFTR）突变）的支气管上皮细胞如何应对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体和严重急性呼吸综合征冠状病毒（SARS-CoV）的感染。基于CF患者因甲型流感病毒（IAV）感染而发病率升高的证据，纳入了与IAV的比较。我们的研究结果表明，无论CFTR突变类型、SARS-CoV-2变体以及原始的2003年SARS-CoV如何，CF上皮细胞中SARS-CoV-2的复制均减少。相比之下，这些细胞中IAV的复制比非CF细胞更有效。有趣的是，CF患者对SARS-CoV-2的易感性降低与血管紧张素转换酶2（ACE2）受体的表达或CFTR功能障碍无关，因为恢复CFTR功能的药物治疗并未使病毒反应正常化。SARS-CoV-2感染和CFTR功能均影响某些细胞因子和趋化因子的浓度，尽管这些影响并不相关。总体而言，本研究揭示了CF上皮细胞中独特的病毒反应，其特征是对某些病毒（如SARS-CoV-2）的复制减少，而对其他病毒（如IAV）的易感性增加。这项研究为CF与病毒的相互作用提供了新的视角，强调需要进一步研究这些差异背后的机制。
