Department of Microbiology and Immunology.
Department of Pediatrics.
Am J Respir Cell Mol Biol. 2020 Jan;62(1):104-111. doi: 10.1165/rcmb.2018-0304OC.
Although chronic bacterial infections and inflammation are associated with progressive lung disease in patients with cystic fibrosis (CF), much less is known regarding the contributions of respiratory viral infections to this process. Clinical studies suggest that antiviral host defenses may be compromised in individuals with CF, and CF airway epithelia exhibit impaired antiviral responses . Here, we used the CF pig model to test the hypothesis that the antiviral activity of respiratory secretions is reduced in CF. We developed an assay to measure the innate antiviral activity present in airway surface liquid (ASL) from CF and non-CF pigs. We found that tracheal and nasal ASL from newborn non-CF pigs exhibited dose-dependent inhibitory activity against several enveloped and encapsidated viruses, including Sendai virus, respiratory syncytial virus, influenza A, and adenovirus. Importantly, we found that the anti-Sendai virus activity of nasal ASL from newborn CF pigs was significantly diminished relative to non-CF littermate controls. This diminution of extracellular antiviral defenses appears to be driven, at least in part, by the differences in pH between CF and non-CF ASL. These data highlight the novel antiviral properties of native airway secretions and suggest the possibility that defects in extracellular antiviral defenses contribute to CF pathogenesis.
尽管慢性细菌感染和炎症与囊性纤维化（CF）患者的肺部进行性疾病有关，但对于呼吸道病毒感染对这一过程的贡献知之甚少。临床研究表明，CF 个体的抗病毒宿主防御可能受损，CF 气道上皮表现出受损的抗病毒反应。在这里，我们使用 CF 猪模型来检验假设，即 CF 中呼吸道分泌物的抗病毒活性降低。我们开发了一种测定法来测量气道表面液体（ASL）中存在的先天抗病毒活性，该液体来自 CF 和非 CF 猪。我们发现，新生非 CF 猪的气管和鼻 ASL 对几种包膜和囊膜病毒（包括仙台病毒、呼吸道合胞病毒、甲型流感病毒和腺病毒）表现出剂量依赖性抑制活性。重要的是，我们发现，与非 CF 同窝对照组相比，新生 CF 猪的鼻 ASL 对仙台病毒的抗病毒活性明显降低。细胞外抗病毒防御的这种减弱似乎至少部分是由 CF 和非 CF ASL 之间的 pH 值差异驱动的。这些数据突出了天然气道分泌物的新型抗病毒特性，并表明细胞外抗病毒防御缺陷可能导致 CF 发病机制。
