Article

Bartlett, N.W. et al. Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Nat. Med. 14, 199-204

Department of Respiratory Medicine, UK National Heart and Lung Institute, and Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, Norfolk Place, London W2 1PG, UK.
Nature medicine (Impact Factor: 27.36). 03/2008; 14(2):199-204. DOI: 10.1038/nm1713
Source: PubMed

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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    • "Previous studies have shown that neutrophil numbers in the lung are correlated with functional impairments in parencyhmal mechanics, [55, 56] possibly due to increased free neutrophil elastase. Related studies in mice infected as adults [8, 10] or neonates [17] have shown additive effects of sensitisation and challenge with ovalbumin and HRV-1B infection on respiratory system resistance (R rs ). Unfortunately, these studies do not compare sexes, nor do they partition respiratory system impedance into airway and parenchymal compartments . "
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    • "Indeed, rhinovirus infection induces the production of cytokines and chemokines including interleukin-6 (IL-6), interleukin-8 (IL-8), regulated on activation normal T cell expressed and secreted (RANTES), interleukin-10 (IL-10) and interferon-b in vivo and in vitro (Bartlett et al., 2008; Message et al., 2008; Subauste et al., 1995; Zhu et al., 1996). The production of most cytokines and chemokines is HRV replication dependent (Bartlett et al., 2008), has pro-inflammatory effects and correlates with the severity of cold symptoms (Gern et al., 2002). Moreover, rhinovirus infection of both primary bronchial epithelial cells and a respiratory epithelial cell line markedly increases cell surface expression of intercellular adhesion molecule-1 (ICAM-1) (Papi and Johnston, 1999) the cellular receptor for the major group (90%) of rhinoviruses (Greve et al., 1989; Uncapher et al., 1991). "
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    • "SPLUNC1 KO and control mice (8–12 weeks old) were anesthetized by intra-peritoneal (i.p.) injection of ketamine (80 mg/kg) and xylazine (10 mg/kg), and intranasally inoculated with HRV-1B at 5×106 pfu/mouse as HRV-1B is the only HRV that can directly infect mouse lungs [32]. After 24 h, the left lung was homogenized for examining HRV RNA levels by quantitative real-time RT-PCR. "
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