Respiratory syncytial virus induces pneumonia, cytokine response, airway obstruction, and chronic inflammatory infiltrates associated with long-term airway hyperresponsiveness in mice.
BACKGROUND
Respiratory syncytial virus (RSV) infection is associated with acute morbidity (e.g., pneumonia and airway obstruction [AO]) and long-term complications (e.g., airway hyperresponsiveness [AHR]). We present a comprehensive evaluation of the acute and chronic phases of RSV respiratory tract infection, using a mouse model.


METHODS
BALB/c mice were inoculated with RSV and monitored for 154 days. RSV loads and cytokines were measured in bronchoalveolar lavage (BAL) samples. Pneumonia severity was assessed using a standard histopathologic score, and pulmonary function was determined by plethysmography.


RESULTS
RSV-infected mice exhibited viral replication that peaked on day 4-5 and became undetectable by day 7. These mice developed acute pneumonia (peak days, 4-5) and chronic pulmonary inflammatory infiltrates that lasted up to 154 days after inoculation. BAL concentrations of tumor necrosis factor- alpha, interleukin (IL)-6, interferon- gamma, IL-4, IL-10, KC (an IL-8 homologue), MIG (CXCL9), RANTES, macrophage inflammatory protein-1 alpha, and eotaxin were significantly higher in RSV-infected mice than in control mice. RSV-infected mice developed acute AO during the first week of infection that persisted for 42 days. RSV-infected mice also showed significant AHR in response to methacholine up to 154 days.


CONCLUSIONS
This model provides a means to investigate the immunopathogenesis of RSV infection and its association with reactive airway disease.
Jafri
Hasan S
HS
Department of Pediatrics, Division of Infectious Diseases, The University of Texas Southwestern Medical Center at Dallas, Texas, USA. hasan.jafri@utsouthwestern.edu
Chavez-Bueno
Susana
S
Mejias
Asuncion
A
Gomez
Ana M
AM
Rios
Ana M
AM
Nassi
Shahryar S
SS
Yusuf
Munira
M
Kapur
Payal
P
Hardy
Robert D
RD
Hatfield
Jeanine
J
Rogers
Beverly B
BB
Krisher
Karen
K
Ramilo
Octavio
O
D000402:Airway Obstruction / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010993:Plethysmography, Whole Body; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric
D016207:Cytokines