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


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.


  1. 1

    Lemanske, R.F., Jr. et al. Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J. Allergy Clin. Immunol. 116, 571–577 (2005).

    Article  Google Scholar 

  2. 2

    Kaiser, L. et al. Chronic rhinoviral infection in lung transplant recipients. Am. J. Respir. Crit. Care Med. 174, 1392–1399 (2006).

    Article  Google Scholar 

  3. 3

    Johnston, S.L. et al. Community study of role of viral infections in exacerbations of asthma in 9–11 year old children. Br. Med. J. 310, 1225–1229 (1995).

    CAS  Article  Google Scholar 

  4. 4

    Corne, J.M. et al. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet 359, 831–834 (2002).

    Article  Google Scholar 

  5. 5

    Chauhan, A.J. et al. Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children. Lancet 361, 1939–1944 (2003).

    CAS  Article  Google Scholar 

  6. 6

    Grissell, T.V. et al. Interleukin-10 gene expression in acute virus-induced asthma. Am. J. Respir. Crit. Care Med. 172, 433–439 (2005).

    Article  Google Scholar 

  7. 7

    Papi, A. et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am. J. Respir. Crit. Care Med. 173, 1114–1121 (2006).

    Article  Google Scholar 

  8. 8

    Bertino, J.S. Cost burden of viral respiratory infections: issues for formulary decision makers. Am. J. Med. 112 (Suppl. 6A), 42S–49S (2002).

    Article  Google Scholar 

  9. 9

    Lomax, N.B. & Yin, F.H. Evidence for the role of the P2 protein of human rhinovirus in its host range change. J. Virol. 63, 2396–2399 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Tuthill, T.J. et al. Mouse respiratory epithelial cells support efficient replication of human rhinovirus. J. Gen. Virol. 84, 2829–2836 (2003).

    CAS  Article  Google Scholar 

  11. 11

    Greve, J.M. et al. The major human rhinovirus receptor is ICAM-1. Cell 56, 839–847 (1989).

    CAS  Article  Google Scholar 

  12. 12

    Register, R.B., Uncapher, C.R., Naylor, A.M., Lineberger, D.W. & Colonno, R.J. Human-murine chimeras of ICAM-1 identify amino acid residues critical for rhinovirus and antibody binding. J. Virol. 65, 6589–6596 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Staunton, D.E., Gaur, A., Chan, P.Y. & Springer, T.A. Internalization of a major group human rhinovirus does not require cytoplasmic or transmembrane domains of ICAM-1. J. Immunol. 148, 3271–3274 (1992).

    CAS  PubMed  Google Scholar 

  14. 14

    Liao, F. et al. CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3α. J. Immunol. 162, 186–194 (1999).

    CAS  PubMed  Google Scholar 

  15. 15

    Nakayama, T. et al. Inducible expression of a CC chemokine liver- and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3 alpha/CCL20 by epidermal keratinocytes and its role in atopic dermatitis. Int. Immunol. 13, 95–103 (2001).

    CAS  Article  Google Scholar 

  16. 16

    Fraenkel, D.J. et al. Lower airways inflammation during rhinovirus colds in normal and in asthmatic subjects. Am. J. Respir. Crit. Care Med. 151, 879–886 (1995).

    CAS  PubMed  Google Scholar 

  17. 17

    Grunberg, K. et al. Experimental rhinovirus 16 infection. Effects on cell differentials and soluble markers in sputum in asthmatic subjects. Am. J. Respir. Crit. Care Med. 156, 609–616 (1997).

    CAS  Article  Google Scholar 

  18. 18

    Inoue, D. et al. Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells. Respir. Physiol. Neurobiol. 154, 484–499 (2006).

    CAS  Article  Google Scholar 

  19. 19

    Wark, P.A. et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J. Exp. Med. 201, 937–947 (2005).

    CAS  Article  Google Scholar 

  20. 20

    Contoli, M. et al. Role of deficient type III interferon-λ production in asthma exacerbations. Nat. Med. 12, 1023–1026 (2006).

    CAS  Article  Google Scholar 

  21. 21

    Ank, N. et al. Lambda interferon (IFN-λ), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J. Virol. 80, 4501–4509 (2006).

    CAS  Article  Google Scholar 

  22. 22

    Bartlett, N.W., Buttigieg, K., Kotenko, S.V. & Smith, G.L. Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model. J. Gen. Virol. 86, 1589–1596 (2005).

    CAS  Article  Google Scholar 

  23. 23

    Harris, J.R. & Racaniello, V.R. Changes in rhinovirus protein 2C allow efficient replication in mouse cells. J. Virol. 77, 4773–4780 (2003).

    CAS  Article  Google Scholar 

  24. 24

    Harris, J.R. & Racaniello, V.R. Amino acid changes in proteins 2B and 3A mediate rhinovirus type 39 growth in mouse cells. J. Virol. 79, 5363–5373 (2005).

    CAS  Article  Google Scholar 

  25. 25

    Wark, P.A. & Gibson, P.G. Asthma exacerbations. 3: Pathogenesis. Thorax 61, 909–915 (2006).

    CAS  Article  Google Scholar 

  26. 26

    Groneberg, D.A. et al. Expression of respiratory mucins in fatal status asthmaticus and mild asthma. Histopathology 40, 367–373 (2002).

    CAS  Article  Google Scholar 

  27. 27

    Murray, C.S. et al. Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax 61, 376–382 (2006).

    CAS  Article  Google Scholar 

  28. 28

    Green, R.M. et al. Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. Br. Med. J. 324, 763 (2002).

    Article  Google Scholar 

  29. 29

    Hewson, C.A., Jardine, A., Edwards, M.R., Laza-Stanca, V. & Johnston, S.L. Toll-like receptor 3 is induced by and mediates antiviral activity against rhinovirus infection of human bronchial epithelial cells. J. Virol. 79, 12273–12279 (2005).

    CAS  Article  Google Scholar 

  30. 30

    Murphy, B.R., Prince, G.A., Lawrence, L.A., Croen, K.D. & Collins, P.L. Detection of respiratory syncytial virus (RSV) infected cells by in situ hybridization in the lungs of cotton rats immunized with formalin-inactivated virus or purified RSV F and G glycoprotein subunit vaccine and challenged with RSV. Virus Res. 16, 153–162 (1990).

    CAS  Article  Google Scholar 

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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).

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