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15 June 2006

Volume 193, Number 12
The Journal of Infectious Diseases 2006;193:1634–1642
© 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2006/19312-0005$15.00
DOI: 10.1086/504262
MAJOR ARTICLE

Human Metapneumovirus Infection Induces Long‐Term Pulmonary Inflammation Associated with Airway Obstruction and Hyperresponsiveness in Mice

Marie‐Ève Hamelin,1

Gregory A. Prince,3

Ana M. Gomez,4

Richard Kinkead,2 and

Guy Boivin1

1Research Center in Infectious Diseases and 2Department of Pediatrics, Centre Hospitalier Universitaire de Québec and Laval University, Québec City, Québec, Canada; 3Virion Systems, Inc., Rockville, Maryland; 4Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas

Background.Human metapneumovirus (hMPV) is a newly described paramyxovirus that is associated with bronchiolitis, pneumonia, and asthma exacerbation. The objective of the present work was to study the duration of pulmonary inflammation and the functional consequences of infection with hMPV by use of a BALB/c mouse model.

Methods.BALB/c mice were inoculated with TCID50 of hMPV type A (C‐85473), and viral persistence in lungs was assessed by reverse‐transcription polymerase chain reaction for 154 days after infection. Pulmonary inflammation was characterized in histopathological experiments by use of a validated scoring system, and periodic acid–Schiff (PAS) staining of lung sections was used to document increased mucus production, also until day 154. Finally, respiratory functions were analyzed by taking plethysmographic measurements until day 70.

Results.Persistence of viral RNA and significant pulmonary inflammation were noted until day 154, whereas the findings for PAS staining suggested that mucus production was increased only until day 12. Maximal breathing difficulties occurred on day 5, and airway obstruction and hyperresponsiveness were still significant until at least day 70.

Conclusion.Acute hMPV infection in BALB/c mice is associated with long‐term pulmonary inflammation that leads to significant obstructive disease of the airways. This animal model will be of a great benefit in the evaluation of novel therapeutic and prophylactic modalities.

Received 8 September 2005; accepted 19 January 2006; electronically published 11 May 2006.

Reprints or correspondence: Dr. Guy Boivin, CHUQ‐CHUL, Room RC‐709, 2705 Blvd. Laurier, Sainte‐Foy, Québec, Canada G1V 4G2 ().

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  • Potential conflicts of interest: none reported.

    Financial support: Canadian Institutes of Health Research (research grant CIHR‐MOP‐62789); Le Fonds de la Recherche en Santé du Québec (FRSQ)–Respiratory Health Network (research grant to G.B.). G.B. is a senior research scholar of the FRSQ and holds the Canada Research Chair in Emerging Viruses; M.‐E.H. has received a Ph.D. scholarship from the FRSQ; and R.K. holds the Canada Research Chair in Respiratory Neurobiology.

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