Airway Surface Liquid Has Innate Antiviral Activity That Is Reduced in Cystic Fibrosis
Airway Surface Liquid Has Innate Antiviral Activity That Is Reduced in Cystic Fibrosis
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DOI：
10.1165/rcmb.2018-0304oc
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发表时间：
2020-01-01
影响因子：
6.4
通讯作者：
McCray, Paul B., Jr.
中科院分区：
文献类型：
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作者：
Berkebile, Abigail R.;Bartlett, Jennifer A.;McCray, Paul B., Jr.
虽然慢性细菌感染和炎症与囊性纤维化患者的进行性肺部疾病有关，但对呼吸道病毒感染在这一过程中的作用知之甚少。临床研究表明，慢性阻塞性肺疾病患者的抗病毒宿主防御功能可能受损，体外培养的慢性阻塞性肺疾病患者的呼吸道上皮细胞抗病毒反应受损。在这里，我们使用猪慢性萎缩性胃炎模型来检验假设，即呼吸道分泌物的抗病毒活性在慢性萎缩性胃炎中降低。我们建立了一种体外检测方法来检测CF型和非CF型猪的呼吸道表面液体(ASL)中存在的天然抗病毒活性。我们发现新生猪的气管和鼻腔ASL对包括仙台病毒、呼吸道合胞病毒、甲型流感病毒和腺病毒在内的几种被包裹和被包裹的病毒具有剂量依赖的抑制活性。重要的是，我们发现新生CF仔猪鼻腔ASL的抗仙台病毒活性显著低于非CF仔猪。这种细胞外抗病毒防御能力的减弱似乎至少部分是由CFASL和非CFASL之间的pH差异所驱动的。这些数据强调了天然呼吸道分泌物的新的抗病毒特性，并提示细胞外抗病毒防御系统的缺陷可能与CF的发病有关。
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 in vitro. 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 in vitro 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.