Key result
Attenuated mengovirus inhalation drives respiratory infection and lower airway inflammation in rats versus inactive virus.
Attenuated mengovirus causes a respiratory infection in rats with viral shedding and neutrophilic inflammation, providing a useful rodent model for rhinovirus-induced airway inflammation.
No clinical implications yet; leaves open a rodent model for rhinovirus airway inflammation research.
BACKGROUND: 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. 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. RESULTS: After inoculation with 10(7) 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. CONCLUSION: Attenuated 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.
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Rosenthal et al. (2009) studied Picornavirus-induced airway infection and inflammation. Attenuated mengovirus (vMC0) vs. Vehicle or UV-inactivated virus was evaluated on Recovery of infectious virus and lower airway inflammation (neutrophils and lymphocytes) (p=<0.05). Inhalation of attenuated mengovirus in rats caused a respiratory infection with several days of viral shedding and significant increases in lower airway neutrophils, lymphocytes, and chemokines compared to vehicle or UV-inactivated virus.
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