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

Nature Medicine volume 14, pages 199–204 (2008)Cite this article

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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Author notes

  1. Patrick Jourdan, Jerome Burnet & Edward D Blair

    Present address: Present addresses: Integrated Medicines, Topfield House, Ermine Street, Caxton, Cambridge CB3 8PQ, UK (E.D.B.); Labtech France, 13 rue Titon, 75011 Paris, France (P.J.); Molecular Oncology Unit, John Vane Science Center, Charterhouse Square, London EC1M 6BQ, UK (J.B.).,

  2. Nathan W Bartlett and Ross P Walton: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory Medicine, UK National Heart and Lung Institute, Wright Fleming Institute of Infection and Immunity, and Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, Norfolk Place, London, W2 1PG, UK

    Nathan W Bartlett, Ross P Walton, Michael R Edwards, Juliya Aniscenko, Nicholas Glanville, Patrick Jourdan, Jerome Burnet, Jurgen Schwarze & Sebastian L Johnston

  2. Research Centre on Asthma and Chronic Obstructive Pulmonary Disease, University of Ferrara, Ferrara, 44100, Italy

    Gaetano Caramori & Alberto Papi

  3. Department of Population Genetics and Gene Therapy, National Heart and Lung Institute, Imperial College London, Royal Brompton Campus, London, SW3 6NP, UK

    Jie Zhu & Peter K Jeffery

  4. Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, South Kensington, London, SW7 2AZ, UK

    Katherine J Choy & Clare M Lloyd

  5. Institute for Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK

    Tobias J Tuthill, Richard A Killington & David J Rowlands

  6. GlaxoSmithKline Medicines Research Centre, Stevenage, SG1 2NY, UK

    Michael S Pedrick, Michael J Hurle, Chris Plumpton, Nigel A Sharp, James N Bussell, Edward D Blair & Neil J Clarke

  7. Department of Biology, The Galton Laboratory, University College London, London, WC1E 6BT, UK

    Dallas M Swallow

  8. Sanofi Pasteur, S.A., Avenue Pont Pasteur, Lyon, 69007, France

    Bruno Guy & Jeffrey W Almond

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  1. Nathan W Bartlett
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Contributions

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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