A rat model of picornavirus-induced airway infection and inflammation.
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.


CONCLUSIONS
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.
Rosenthal
Louis A
LA
Department of Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA. lar@medicine.wisc.edu
Amineva
Svetlana P
SP
Szakaly
Renee J
RJ
Lemanske
Robert F
RF
Gern
James E
JE
Sorkness
Ronald L
RL
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008574:Mengovirus / Q000276:immunology / Q000472:pathogenicity*; D009504:Neutrophils / Q000276:immunology; D010850:Picornaviridae Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D051381:Rats; D012141:Respiratory Tract Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D017201:Virus Shedding