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.

Colasurdo GN ，Fullmer JJ ，Elidemir O ，Atkins C ，Khan AM ，Stark JM ... -  《JOURNAL OF MEDICAL VIROLOGY》

Immune and functional role of nitric oxide in a mouse model of respiratory syncytial virus infection.

Stark JM ，Khan AM ，Chiappetta CL ，Xue H ，Alcorn JL ，Colasurdo GN ... -  《JOURNAL OF INFECTIOUS DISEASES》

Role of cysteinyl leukotrienes in airway inflammation and responsiveness following RSV infection in BALB/c mice.

Fullmer JJ ，Khan AM ，Elidemir O ，Chiappetta C ，Stark JM ，Colasurdo GN ... -  《PEDIATRIC ALLERGY AND IMMUNOLOGY》

MIP-1alpha is produced but it does not control pulmonary inflammation in response to respiratory syncytial virus infection in mice.

The intent of this study was to compare the cellular and biochemical inflammatory responses of mice infected with the paramyxovirus pathogens respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM). Although RSV is not a natural pathogen of mice, it has been used extensively in mouse models of the human disease, as a limited respiratory infection can be established via intranasal inoculation of virus at high titer. In earlier work, we found that acute infection with the natural rodent pathogen, PVM, elicited a rapid and sustained pulmonary inflammatory response (peak, 1.7 x 10(6) leukocytes/ml BAL fluid) that was dependent on both local production of MIP-1alpha and signaling via its receptor, CCR1. We find here that MIP-1alpha is also produced in response to RSV, although relatively few leukocytes (<200 ml BAL fluid) are recruited to the lungs in response. Further experiments with CCR1-deficient mice confirm the finding that although MIP-1alpha is produced in response to RSV infection, leukocytes do not respond via this pathway. Among the explanations for these findings, we propose that there are other, as yet to be identified proinflammatory mediators elicited in response to PVM (but not in response to RSV) that serve to prime the leukocytes in vivo, thus enabling them to respond to MIP-1alpha signaling via CCR1. Furthermore, the differences in disease pathogenesis seen in response to each of these pneumovirus infections in mice raise questions regarding the extent to which primary RSV infection in mice can be used as a model of primary RSV infection in humans.

Domachowske JB ，Bonville CA ，Gao JL ，Murphy PM ，Easton AJ ，Rosenberg HF ... -  《CELLULAR IMMUNOLOGY》

Effects of primary and secondary low-grade respiratory syncytial virus infections in a murine model of asthma.

Kondo Y ，Matsuse H ，Machida I ，Kawano T ，Saeki S ，Tomari S ，Obase Y ，Fukushima C ，Kohno S ... -  《CLINICAL AND EXPERIMENTAL ALLERGY》