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Journal of Virology, July 2005, p. 8894-8903, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.8894-8903.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Pathogenesis of Human Metapneumovirus Lung Infection in BALB/c Mice and Cotton Rats

Marie-Ève Hamelin,1* Kevin Yim,2 Katie H. Kuhn,2 Rose P. Cragin,2 Marina Boukhvalova,2 Jorge C. G. Blanco,2 Gregory A. Prince,2 and Guy Boivin1*

Research Center in Infectious Diseases of the Centre Hospitalier Universitaire de Québec, and Laval University, Québec City, Québec, Canada,1 Virion Systems, Inc., Rockville, Maryland2

Received 26 November 2004/ Accepted 22 March 2005

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 108 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 107 TCID50/g lung) and cotton rats (mean of 1.03 x 105 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 1{alpha}, 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.

* Corresponding author. Mailing address: CHUQ-CHUL, Room RC-709, 2705 Blvd. Laurier, Sainte-Foy, Québec, Canada G1V 4G2. Phone: (418) 654-2705. Fax: (418) 654-2715. E-mail for Guy Boivin: Guy.Boivin{at}crchul.ulaval.ca. E-mail for Marie-Ève Hamelin: Marie-eve.Hamelin{at}crchul.ulaval.ca.

Journal of Virology, July 2005, p. 8894-8903, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.8894-8903.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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