Abstract
The respiratory Influenza A Viruses (IAVs) and emerging zoonotic viruses such as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pose a significant threat to human health. To accelerate our understanding of the host–pathogen response to respiratory viruses, the use of more complex in vitro systems such as normal human bronchial epithelial (NHBE) cell culture models has gained prominence as an alternative to animal models. NHBE cells were differentiated under air-liquid interface (ALI) conditions to form an in vitro pseudostratified epithelium. The responses of well-differentiated (wd) NHBE cells were examined following infection with the 2009 pandemic Influenza A/H1N1pdm09 strain or following challenge with the dsRNA mimic, poly(I:C). At 30 h postinfection with H1N1pdm09, the integrity of the airway epithelium was severely impaired and apical junction complex damage was exhibited by the disassembly of zona occludens-1 (ZO-1) from the cell cytoskeleton. wdNHBE cells produced an innate immune response to IAV-infection with increased transcription of pro- and anti-inflammatory cytokines and chemokines and the antiviral viperin but reduced expression of the mucin-encoding MUC5B, which may impair mucociliary clearance. Poly(I:C) produced similar responses to IAV, with the exception of MUC5B expression which was more than 3-fold higher than for control cells. This study demonstrates that wdNHBE cells are an appropriate ex-vivo model system to investigate the pathogenesis of respiratory viruses.
Highlights
Over the past 30 years, there has been a rapid rise in emerging infectious diseases both of zoonotic and human origin [1]
Cells cultured at air-liquid interface (ALI) on collagen I-coated transwells formed a polarized, pseudostratified epithelium around four weeks postairlift. wdNHBE cells exhibited a mucociliary phenotype, characterized by the secretion of mucus on the apical surface and the coordinated beating of cilia on the surface of ciliated cells (Video S1)
The disruption of the airway epithelium by Influenza A Viruses (IAVs) H1N1pdm09 and poly(I:C), plus the induction of the innate immune response and antiviral, and pro- and anti-inflammatory genes demonstrated the viability of this model to investigate pandemic influenza
Summary
Over the past 30 years, there has been a rapid rise in emerging infectious diseases both of zoonotic and human origin [1]. The recent emergence and worldwide spread of the Severe Acute. Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) virus which produces the Coronavirus disease. Respiratory RNA viruses, influenza A viruses (IAV) of the Orthomyxoviridae family are a major pandemic risk as they replicate rapidly, lack a proof-reading mechanism, have a high mutation rate and are readily transmissible [3,5,6,7]. Over 100 years ago, the 1918 H1N1 “Spanish flu” pandemic killed up to 50 million people worldwide [8,9,10]. Three global influenza pandemics have occurred since, “Asian flu” H2N2
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