TY - JOUR
T1 - Respiratory syncytial virus induces pneumonia, cytokine response, airway obstruction, and chronic inflammatory infiltrates associated with long-term airway hyperresponsiveness in mice
AU - Jafri, Hasan S.
AU - Chávez-Bueno, Susana
AU - Mejías, Asunción
AU - Gómez, Ana M.
AU - Ríos, Ana M.
AU - Nassi, Shahryar S.
AU - Yusuf, Munira
AU - Kapur, Payal
AU - Hardy, Robert D.
AU - Hatfield, Jeanine
AU - Rogers, Beverly B.
AU - Krisher, Karen
AU - Ramilo, Octavio
N1 - Funding Information:
Received 18 July 2003; accepted 8 December 2003; electronically published 29 April 2004. Presented in part: 2001 Pediatric Academic Societies annual meeting, Baltimore, 8 April–1 May 2001 (abstract 1357); 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, 27–30 September 2002 (abstract V-477). Financial support: Children’s Medical Center of Dallas Research Foundation (grant to H.S.J.); American Lung Association (grants to O.R. and H.S.J.); GlaxoSmithKline Pharmaceuticals (Pediatric Infectious Disease Society Fellowship Award to S.C.-B.). a H.S.J. and S.C.-B. made equal contributions to the article. Reprints or correspondence: Dr. Hasan Jafri, UT Southwestern Medical Center at Dallas, Dept. of Pediatrics, Div. of Pediatric Infectious Diseases, 5323 Harry Hines Blvd., Dallas, TX 75390-9063 (hasan.jafri@utsouthwestern.edu).
PY - 2004/5/15
Y1 - 2004/5/15
N2 - 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-α, interleukin (IL)-6, interferon-γ, IL-4, IL-10, KC (an IL-8 homologue), MIG (CXCL9), RANTES, macrophage inflammatory protein-1α, 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. Conclusion. This model provides a means to investigate the immunopathogenesis of RSV infection and its association with reactive airway disease.
AB - 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-α, interleukin (IL)-6, interferon-γ, IL-4, IL-10, KC (an IL-8 homologue), MIG (CXCL9), RANTES, macrophage inflammatory protein-1α, 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. Conclusion. This model provides a means to investigate the immunopathogenesis of RSV infection and its association with reactive airway disease.
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U2 - 10.1086/386372
DO - 10.1086/386372
M3 - Article
C2 - 15122522
AN - SCOPUS:2542419993
SN - 0022-1899
VL - 189
SP - 1856
EP - 1865
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 10
ER -