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.

Rhinovirus infections and immunisation induce cross-serotype reactive antibodies to VP1

“…Serotypes RV1B, RV29 and RV16 were produced by culture in HeLa cells as described previously (Bartlett et al, 2008). To investigate virus-specificity of antibody binding, control HeLa lysate was prepared in an identical fashion from uninfected cells.…”

“…To investigate virus-specificity of antibody binding, control HeLa lysate was prepared in an identical fashion from uninfected cells. RV preparations were inactivated by exposing them to UV light (1,200 mJ/cm2 for 30 min) as previously described (Bartlett et al, 2008). Recombinant VP1 from RV14 and RV89 was expressed and purified as described (Edlmayr et al, 2009(Edlmayr et al, , 2011.…”

“…Female 6-8 week old BALB/c mice were purchased from Harlan and housed under appropriate SPF conditions. RV infections were performed as described previously (Bartlett et al, 2008). Briefly, purified RV (1x10 6 TCID 50 ) in a 50lL volume of PBS was introduced i.n.…”

“…Recently a mouse model of RV infection was developed (Bartlett et al, 2008). Intranasal infection of minor (BALB/c) and major group (transgenic BALB/c expressing mouse-human ICAM-1 chimaera) RV induced airway inflammatory responses and viral replication was demonstrated in airway epithelium (Bartlett et al, 2008).…”

“…Recently a mouse model of RV infection was developed (Bartlett et al, 2008). Intranasal infection of minor (BALB/c) and major group (transgenic BALB/c expressing mouse-human ICAM-1 chimaera) RV induced airway inflammatory responses and viral replication was demonstrated in airway epithelium (Bartlett et al, 2008). The major advantage of using a mouse model of RV infection for our studies is, unlike humans, mice are immunologically naive to RV and the development of the humoral immune responses can be directly studied without interference from cross reactive antibodies.…”