Human metapneumovirus infection induces long-term pulmonary inflammation associated with airway obstruction and hyperresponsiveness in mice.
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 1 x 10(8) TCID(50) 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.


CONCLUSIONS
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.
Hamelin
Marie-Eve
ME
Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Québec, Laval University, Quebec City, Quebec, Canada.
Prince
Gregory A
GA
Gomez
Ana M
AM
Kinkead
Richard
R
Boivin
Guy
G
D000818:Animals; D004195:Disease Models, Animal; D006651:Histocytochemistry; D008168:Lung / Q000473:pathology / Q000821:virology; D008173:Lung Diseases, Obstructive / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D029121:Metapneumovirus; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus; D018184:Paramyxoviridae Infections / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D010503:Periodic Acid-Schiff Reaction; D010993:Plethysmography, Whole Body; D011024:Pneumonia, Viral / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012367:RNA, Viral