Pathogenesis of human metapneumovirus lung infection in BALB/c mice and cotton rats.
Human metapneumovirus (hMPV) is a newly described member of the Paramyxoviridae family causing acute respiratory tract infections, especially in young children. We studied the pathogenesis of this viral infection in two experimental small animal models (BALB/c mice and cotton rats). Significant viral replication in the lungs of both animals was found following an intranasal challenge of 10(8) 50% tissue culture infectious doses (TCID50) and persisted for <2 and <3 weeks in the case of cotton rats and mice, respectively. Peak viral loads were found on day 5 postinfection in both mice (mean of 1.92 x 10(7) TCID50/g lung) and cotton rats (mean of 1.03 x 10(5) TCID50/g). Clinical symptoms consisting of breathing difficulties, ruffled fur, and weight loss were noted in mice only around the time of peak viral replication. Most significant pulmonary inflammatory changes and peak expression of macrophage inflammatory protein 1alpha, gamma interferon, and RANTES occurred at the time of maximal viral replication (day 5) in both models. Cellular infiltration occurred predominantly around and within alveoli and persisted for at least 21 days in mice, whereas it was more limited in time with more peribronchiolitis in cotton rats. Both animal models would be of great value in evaluating different therapeutic agents, as well as vaccine candidates against hMPV.
Research Center in Infectious Diseases of the Centre Hospitalier Universitaire de Québec, and Laval University, Québec City, Canada.
Marie-Eve
ME
Hamelin
Kevin
K
Yim
Katie H
KH
Kuhn
Rose P
RP
Cragin
Marina
M
Boukhvalova
Jorge C G
JC
Blanco
Gregory A
GA
Prince
Guy
G
Boivin
D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology / Q000821:virology*; D029121:Metapneumovirus / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D016205:Sigmodontinae
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D015847:Interleukin-4; D007371:Interferon-gamma