Abstract
BackgroundInfection of the lower airways by rhinovirus, a member of the picornavirus family, is an important cause of wheezing illnesses in infants, and plays an important role in the pathogenesis of rhinovirus-induced asthma exacerbations. Given the absence of natural rhinovirus infections in rodents, we investigated whether an attenuated form of mengovirus, a picornavirus whose wild-type form causes systemic rather than respiratory infections in its natural rodent hosts, could induce airway infections in rats with inflammatory responses similar to those in human rhinovirus infections.ResultsAfter inoculation with 107 plaque-forming units of attenuated mengovirus through an inhalation route, infectious mengovirus was consistently recovered on days 1 and 3 postinoculation from left lung homogenates (median Log10 plaque-forming units = 6.0 and 4.8, respectively) and right lung bronchoalveolar lavage fluid (median Log10 plaque-forming units = 5.8 and 4.0, respectively). Insufflation of attenuated mengovirus, but not vehicle or UV-inactivated virus, into the lungs of BN rats caused significant increases (P < 0.05) in lower airway neutrophils and lymphocytes in the bronchoalveolar lavage fluid and patchy peribronchiolar, perivascular, and alveolar cellular infiltrates in lung tissue sections. In addition, infection with attenuated mengovirus significantly increased (P < 0.05) lower airway levels of neutrophil chemoattractant CXCR2 ligands [cytokine-induced neutrophil chemoattractant-1 (CINC-1; CXCL1) and macrophage inflammatory protein-2 (MIP-2; CXCL2)] and monocyte chemoattractant protein-1 (MCP-1; CCL2) in comparison to inoculation with vehicle or UV-inactivated virus.ConclusionAttenuated mengovirus caused a respiratory infection in rats with several days of viral shedding accompanied by a lower airway inflammatory response consisting of neutrophils and lymphocytes. These features suggest that mengovirus-induced airway infection in rodents could be a useful model to define mechanisms of rhinovirus-induced airway inflammation in humans.
Highlights
Infection of the lower airways by rhinovirus, a member of the picornavirus family, is an important cause of wheezing illnesses in infants, and plays an important role in the pathogenesis of rhinovirus-induced asthma exacerbations
Expression of infectious virus in the lungs after inhalation of attenuated mengovirus To examine whether attenuated mengovirus could induce lower airway infections in rats, 107 plaque-forming units (PFU) of attenuated mengovirus, vMC0, an equivalent amount of UV-inactivated vMC0, or vehicle were insufflated into the lungs of adult BN rats
On days 1 and 3 postinoculation, significant levels of infectious mengovirus were recovered from left lung homogenates and right lung bronchoalveolar lavage (BAL) fluid of BN rats inoculated with the attenuated mengovirus, vMC0 (Figure 1; P < 0.005)
Summary
Infection of the lower airways by rhinovirus, a member of the picornavirus family, is an important cause of wheezing illnesses in infants, and plays an important role in the pathogenesis of rhinovirus-induced asthma exacerbations. Neutrophils are the predominant inflammatory cell initially recruited to the airways during HRV infections [12,13], and clinical studies have demonstrated that there is a positive correlation between this inflammatory response and respiratory symptoms and airway dysfunction [14,15,16,17]. These relationships have been observed in a variety of clinical and experimental infection studies, the nature of this relationship is still enigmatic. Perhaps the difference between a relatively uneventful cold and more severe HRV-induced airway sequelae resides in the balance between beneficial and detrimental effects of the neutrophilic inflammatory response
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