In Vitro Modelling of Respiratory Virus Infections in Human Airway Epithelial Cells – A Systematic Review

Respiratory tract infections (RTI) are a major cause of morbidity and mortality in humans. A large number of RTIs is caused by viruses, often resulting in more severe disease in infants, elderly and the immunocompromised. Upon viral infection, most individuals experience common cold-like symptoms as...

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Published in:Frontiers in immunology Vol. 12; p. 683002
Main Authors: Rijsbergen, Laurine C., van Dijk, Laura L. A., Engel, Maarten F. M., de Vries, Rory D., de Swart, Rik L.
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 18.08.2021
Subjects:
airway modeling
Cell Culture Techniques
Cell Line
Cells, Cultured
co-culture
Coculture Techniques
Disease Susceptibility - immunology
Epithelial Cells - metabolism
Epithelial Cells - virology
Host-Pathogen Interactions
Humans
Immunology
In Vitro Techniques
Organ Specificity
organoid culture
primary airway epithelium culture
Respiratory Mucosa - immunology
Respiratory Mucosa - metabolism
Respiratory Mucosa - virology
Respiratory Tract Infections - metabolism
Respiratory Tract Infections - pathology
Respiratory Tract Infections - virology
respiratory viral diseases
respiratory viral diseases
airway modeling
organoid culture
primary airway epithelium culture
co-culture
ISSN:1664-3224, 1664-3224
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Summary:Respiratory tract infections (RTI) are a major cause of morbidity and mortality in humans. A large number of RTIs is caused by viruses, often resulting in more severe disease in infants, elderly and the immunocompromised. Upon viral infection, most individuals experience common cold-like symptoms associated with an upper RTI. However, in some cases a severe and sometimes life-threatening lower RTI may develop. Reproducible and scalable in vitro culture models that accurately reflect the human respiratory tract are needed to study interactions between respiratory viruses and the host, and to test novel therapeutic interventions. Multiple in vitro respiratory cell culture systems have been described, but the majority of these are based on immortalized cell lines. Although useful for studying certain aspects of viral infections, such monomorphic, unicellular systems fall short in creating an understanding of the processes that occur at an integrated tissue level. Novel in vitro models involving primary human airway epithelial cells and, more recently, human airway organoids, are now in use. In this review, we describe the evolution of in vitro cell culture systems and their characteristics in the context of viral RTIs, starting from advances after immortalized cell cultures to more recently developed organoid systems. Furthermore, we describe how these models are used in studying virus-host interactions, e.g. tropism and receptor studies as well as interactions with the innate immune system. Finally, we provide an outlook for future developments in this field, including co-factors that mimic the microenvironment in the respiratory tract.
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This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology
Reviewed by: Anass Bouchnita, University of Texas at Austin, United States; Antonella Casola, University of Texas Medical Branch at Galveston, United States
Edited by: Nabila Seddiki, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), France
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.683002