Airway surface liquid has innate antiviral activity that is reduced in cystic fibrosis

Abigail R. Berkebile, Jennifer A. Bartlett, Mahmoud Abou Alaiwa, Steven M. Varga, Ultan Power, Paul B. McCray

Research output: Contribution to journalArticle

84 Downloads (Pure)

Abstract

While chronic bacterial infections and inflammation are associated with progressive lung disease in cystic fibrosis (CF) patients, 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 (SeV), respiratory syncytial virus (RSV), influenza A, and adenovirus. Importantly, we found that the anti-SeV 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.
Original languageEnglish
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Early online date26 Jun 2019
DOIs
Publication statusEarly online date - 26 Jun 2019

Fingerprint

Cystic Fibrosis
Antiviral Agents
Viruses
Liquids
Fibrosis
Swine
Sendai virus
Nose
Pulmonary diseases
Newborn Infant
Respiratory Syncytial Viruses
Assays
Virus Diseases
Bacterial Infections
Adenoviridae
Respiratory Tract Infections
Human Influenza
Lung Diseases
Defects
Epithelium

Cite this

Berkebile, Abigail R. ; Bartlett, Jennifer A. ; Alaiwa, Mahmoud Abou ; Varga, Steven M. ; Power, Ultan ; McCray, Paul B. / Airway surface liquid has innate antiviral activity that is reduced in cystic fibrosis. In: American Journal of Respiratory Cell and Molecular Biology. 2019.
@article{75bcb71faf0947f8839b992e1f3fb553,
title = "Airway surface liquid has innate antiviral activity that is reduced in cystic fibrosis",
abstract = "While chronic bacterial infections and inflammation are associated with progressive lung disease in cystic fibrosis (CF) patients, 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 (SeV), respiratory syncytial virus (RSV), influenza A, and adenovirus. Importantly, we found that the anti-SeV 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.",
author = "Berkebile, {Abigail R.} and Bartlett, {Jennifer A.} and Alaiwa, {Mahmoud Abou} and Varga, {Steven M.} and Ultan Power and McCray, {Paul B.}",
year = "2019",
month = "6",
day = "26",
doi = "10.1165/rcmb.2018-0304OC",
language = "English",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",

}

Airway surface liquid has innate antiviral activity that is reduced in cystic fibrosis. / Berkebile, Abigail R.; Bartlett, Jennifer A.; Alaiwa, Mahmoud Abou; Varga, Steven M.; Power, Ultan; McCray, Paul B.

In: American Journal of Respiratory Cell and Molecular Biology, 26.06.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Airway surface liquid has innate antiviral activity that is reduced in cystic fibrosis

AU - Berkebile, Abigail R.

AU - Bartlett, Jennifer A.

AU - Alaiwa, Mahmoud Abou

AU - Varga, Steven M.

AU - Power, Ultan

AU - McCray, Paul B.

PY - 2019/6/26

Y1 - 2019/6/26

N2 - While chronic bacterial infections and inflammation are associated with progressive lung disease in cystic fibrosis (CF) patients, 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 (SeV), respiratory syncytial virus (RSV), influenza A, and adenovirus. Importantly, we found that the anti-SeV 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.

AB - While chronic bacterial infections and inflammation are associated with progressive lung disease in cystic fibrosis (CF) patients, 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 (SeV), respiratory syncytial virus (RSV), influenza A, and adenovirus. Importantly, we found that the anti-SeV 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.

U2 - 10.1165/rcmb.2018-0304OC

DO - 10.1165/rcmb.2018-0304OC

M3 - Article

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

ER -