A rat model of picornavirus-induced airway infection and inflammation
Louis A Rosenthal1, Svetlana P Amineva, Renee J Szakaly
1Department of Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA. lar@medicine.wisc.edu
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.
Insights
An attenuated mengovirus successfully created a respiratory infection in rats, mimicking human rhinovirus-induced airway inflammation. This model shows viral shedding and inflammatory cell infiltration in the lower airways, offering new research avenues.
Area of Science:
- Virology
- Immunology
- Respiratory Medicine
Background:
- Rhinovirus infections cause infant wheezing and asthma exacerbations.
- Rodent models for rhinovirus respiratory infections are lacking.
- Mengovirus, a picornavirus, was studied for its potential to model human rhinovirus infections.
Purpose of the Study:
- To investigate if attenuated mengovirus can induce airway infections in rats.
- To determine if this infection elicits inflammatory responses similar to human rhinovirus infections.
Main Methods:
- Rats were inoculated with attenuated mengovirus via inhalation.
- Viral shedding was quantified in lung homogenates and bronchoalveolar lavage fluid.
- Inflammatory cell counts and cytokine levels in the lower airways were analyzed.
Main Results:
- Infectious mengovirus was recovered from rat lungs for several days post-inoculation.
- Mengovirus infection significantly increased lower airway neutrophils and lymphocytes.
- Key inflammatory mediators, including CXCR2 ligands and MCP-1, were elevated.
Conclusions:
- Attenuated mengovirus establishes a respiratory infection in rats with viral shedding.
- The infection triggers a significant lower airway inflammatory response.
- This rodent model may be valuable for studying rhinovirus-induced airway inflammation.
