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


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.


Available from: Ross P Walton
  • Source
    • "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 . "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: Recent studies have employed animal models to investigate links between rhinovirus infection and allergic airways disease, however, most do not involve early life infection, and none consider the effects of sex on responses. Materials and methods: Here, we infected male and female mice with human rhinovirus 1B (or control) on day 7 of life. Mice were then subjected to 7 weeks of exposure to house-dust-mite prior to assessment of bronchoalveolar inflammation, serum antibodies, lung function, and responsiveness to methacholine. Results: There were significant differences in responses between males and females in most outcomes. In males, chronic house-dust-mite exposure increased bronchoalveolar inflammation, house-dust-mite specific IgG1 and responsiveness of the lung parenchyma, however, there was no additional impact of rhinovirus infection. Conversely, in females, there were additive and synergistic effects of rhinovirus infection and house-dust-mite exposure on neutrophilia, airway resistance, and responsiveness of the lung parenchyma. Conclusions: We conclude that early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice.
    Full-text · Article · Jan 2016 · Experimental Lung Research
  • Source
    • "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). "
    [Show abstract] [Hide abstract] ABSTRACT: Human rhinoviruses (HRV), the cause of common colds, are the most frequent precipitants of acute exacerbation of asthma and chronic obstructive pulmonary disease, as well as causes of other serious respiratory diseases. No vaccine or antiviral agents are available for the prevention or treatment of HRV infection. Resveratrol exerts antiviral effect against different DNA and RNA viruses. The antiviral effect of a new resveratrol formulation containing carboxymethylated glucan was analyzed in H1HeLa cell monolayers and ex vivo nasal epithelia infected with HRV-16. Virus yield was evaluated by plaque assay and expression of viral capsid proteins by Western blot. IL-10, IFN-β, IL-6, IL-8 and RANTES levels were evaluated by ELISA assay. ICAM-1 was assessed by Western blot and immunofluorescence. Resveratrol exerted a high, dose-dependent, antiviral activity against HRV-16 replication and reduced virus-induced secretion of IL-6, IL-8 and RANTES to levels similar to that of uninfected nasal epithelia. Basal levels of IL-6 and RANTES were also significantly reduced in uninfected epithelia confirming an anti-inflammatory effect of the compound. HRV-induced expression of ICAM-1 was reversed by resveratrol. Resveratrol may be useful for a therapeutic approach to reduce HRV replication and virus-induced cytokine/chemokine production. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Aug 2015 · Antiviral research
  • Source
    • "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. "
    [Show abstract] [Hide abstract] ABSTRACT: Background/Objective The use of electronic cigarettes (e-cigarettes) is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV) infection. Methodology/Main Results We examined the effects of e-cigarette liquid (e-liquid) on pro-inflammatory cytokine (e.g., IL-6) production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1) in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.
    Full-text · Article · Sep 2014 · PLoS ONE
Show more