Respiratory syncytial virus infection in a murine model of cystic fibrosis.
Viral respiratory infections play an important role in the development and progression of pulmonary disease in cystic fibrosis (CF). The CF mouse model provides a tool to examine the relationship between the cystic fibrosis transmembrane conductance regulator (CFTR) defect and lung disease. This work investigates the cellular response to a common viral pathogen, respiratory syncytial virus (RSV) in the lung of CF mice. RSV was administered by intranasal inoculation of CFTR(tm1Unc)-Tg(FABPCFTR)1Jaw/J (CFTR-/-) and control mice. At day 5 post infection, viral titers, bronchoalveolar fluid nitrate levels (BALF) cell and differential counts, histology and studies on airway mechanics were performed. CFTR-/- mice had an impaired ability to clear RSV. This was associated with an exaggerated inflammatory response (increased lymphocytes and neutrophils) in BALF of RSV-infected CFTR-/- mice and a decreased ability to generate nitric oxide (NO) (measured as BAL nitrate). Lung histopathology of RSV-infected CFTR-/- mice demonstrated increased inflammation compared to RSV (-) CFTR-/- and control mice (regardless of RSV treatment). The airway response to methacholine was increased by RSV infection in CF mice when compared to controls. The CFTR-/- mouse exhibits an aberrant response to RSV infection. This model should be useful in providing further mechanistic information on the biology of respiratory viruses in mammalian models, and provide new insights into the pathogenesis of airway inflammation in patients with CF.
Department of Pediatrics, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Giuseppe N
GN
Colasurdo
Jason J
JJ
Fullmer
Okan
O
Elidemir
Constance
C
Atkins
Amir M
AM
Khan
James M
JM
Stark
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000821:virology; D002452:Cell Count; D004195:Disease Models, Animal; D007249:Inflammation / Q000503:physiopathology; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D008214:Lymphocytes / Q000166:cytology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D018181:Mice, Inbred CFTR; D009504:Neutrophils / Q000166:cytology; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000096:biosynthesis; D018357:Respiratory Syncytial Virus Infections / Q000503:physiopathology* / Q000821:virology*; D012136:Respiratory Syncytial Viruses
D009566:Nitrates; D016210:Methacholine Chloride; D009569:Nitric Oxide