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Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation

Abstract

Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart. Here we describe three novel mouse models of rhinovirus infection: minor-group rhinovirus infection of BALB/c mice, major-group rhinovirus infection of transgenic BALB/c mice expressing a mouse-human ICAM-1 chimera and rhinovirus-induced exacerbation of allergic airway inflammation. These models have features similar to those observed in rhinovirus infection in humans, including augmentation of allergic airway inflammation, and will be useful in the development of future therapies for colds and asthma exacerbations.

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Figure 1: Live minor-group rhinovirus-1B, but not UV-inactivated rhinovirus-1B or major-group rhinovirus-16, induces airway and lung inflammation and mucin production in BALB/c mice.
Figure 2: Rhinovirus-1B induces neutrophil, dendritic cell and lymphocyte chemoattractant chemokine production and proinflammatory cytokine production.
Figure 3: RV-1B replication and induction of innate (antiviral IFN) and acquired virus-specific cellular and humoral immune responses in BALB/c mice.
Figure 4: Major group rhinovirus-16 infection of transgenic mice expressing a human/mouse ICAM-1 chimeric receptor.
Figure 5: Rhinovirus exacerbates airway inflammation, airway hyper-responsiveness, mucus production, and TH1 and TH2 cytokine responses in a model of acute allergic airway inflammation.

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Acknowledgements

This work was supported by Medical Research Council UK grant number G9824522, GlaxoSmithKline, Sanofi Pasteur and Asthma UK grant numbers 03/073, 04/052, 05/067 and 06/050.

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S.L.J. conceived the studies and was principle investigator; all authors contributed to the design and execution of the experiments, helped draft the manuscript and approved the final version for publication.

Corresponding author

Correspondence to Sebastian L Johnston.

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Supplementary Figs. 1–3 and Supplementary Methods (PDF 755 kb)

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Bartlett, N., Walton, R., Edwards, M. et al. Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Nat Med 14, 199–204 (2008). https://doi.org/10.1038/nm1713

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